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1,2,3,4,6-penta-O-galloyl-β-D- glucopyranose Binds to the N- terminal Metal Binding Region to Inhibit Amyloid β-protein Fibril Formation Natália E. C. de Almeida, † Thanh D. Do, ‡ Nichole E. LaPointe, ¥ Michael Tro, † Stuart C. Feinstein, ¥ Joan-Emma Shea, † Michael T. Bowers †, * † Department of Chemistry and Biochemistry, ¥ Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology, University of California, Santa Barbara, California 93106, United States; ‡ Department of Chemistry and the Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States. S1

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12346-penta-O-galloyl-β-D-glucopyranose

Binds to the N-terminal Metal Binding Region to

Inhibit Amyloid β-protein Fibril Formation

Nataacutelia E C de Almeidadagger Thanh D DoDagger Nichole E LaPointeyen Michael Trodagger Stuart C

Feinsteinyen Joan-Emma Sheadagger Michael T Bowersdagger

dagger Department of Chemistry and Biochemistry yen Neuroscience Research Institute and

Department of Molecular Cellular and Developmental Biology University of California

Santa Barbara California 93106 United States Dagger Department of Chemistry and the Beckman

Institute University of Illinois at Urbana-Champaign Urbana Illinois 61801 United States

Corresponding author Michael T Bowers

Tel +1-805-893-2673 E-mail address bowerschemucsbedu

SUPPPORTING INFORMATION

S1

S1 Materials and Methods

S11 Materials and Sample preparation

Peptide and sample preparation

Full-length Aβ1-40 (DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVV)

and Aβ1-42 (DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA) peptides

were synthesized by N-9-fluorenylmethoxycarnonyl (FMOC) chemistry and further purified

by reverse-phase HPLC Their quality was validated by mass spectrometry and amino acids

analysis as previously described1 The samples were prepared in ammonium acetate buffer

(10 mM pH 74) to the final concentration of 10 μM

Aβ1-11 (DAEFRHDSGYE) and Aβ11-22 (EVHHQKLVFFAE) peptides with free termini

were purchased from GenScrip USA Inc (Piscataway NJ) and their samples prepared in

submicron filtered water (HPLC grade) to the final concentration of 100 microM 12346-penta-

O-galloyl-β-D-glucopyranose (PGG) was purchased from Sigma-Aldrich (St Louis MO

USA) and its sample prepared in water containing 20 (vv) of methanol purchased from

TCI America (Portland OR USA)

Full-length (Aβ1-40 and Aβ1-42) and the Aβ fragments (Aβ1-11 and Aβ11-22) were incubated

with the ligand at 11 and 110 molar ratios and positive controls were performed using the

Aβ solutions without the ligand The Aβ1-40 and Aβ1-42 were incubated without and with PGG

and immediately analyzed by ion mobility spectrometry coupled to mass spectrometry (IMS-

MS) whereas IMS-MS analyses of the Aβ1-11 and Aβ11-22 peptides were performed after 1

week of incubation time Additionally the samples were analyzed by transmission electron

microscopy (TEM) after 2 days and 1 week of incubation time at room temperature for the

full-length and Aβ fragments respectively In this context the samples were adsorbed onto

300 mesh formvarcarbon copper grids (Electron Microscopy Sciences) and after 15 min

excess samples was removed and grids were stained for 1 min with 2 uranyl acetate S2

Additionally Aβ1-42 were incubated for 3 days at room temperature and then PGG was

added at Aβ1-42PGG molar ratios of 11 and 110 After more 2 days of incubation the

mixtures followed to TEM analysis

S12 Methods

S121 Ion mobility spectrometry coupled mass spectrometry (IMS-MS)

Samples were analyzed on a home-built ion mobility spectrometer coupled to a mass

spectrometer composed by a nano-electrospray ionization (nano-ESI) source an ion funnel a

temperature-controlled drift cell and a quadrupole mass filter followed by an electron

multiplier detector2 Briefly the ions were continuously generated by a nano-ESI source

focused and stored in the ion funnel A pulse (10 micros) of ions was injected into a drift cell

filled with 3-5 Torr of helium gas (buffer gas) where they gently passed through under the

influence of a weak electric field Normally the injection energy was kept as ~40 eV to

minimize thermal heating of the ions during the injection process but it can be varied from

~20 to ~150 eV The ions exiting the drift cell were mass analyzed by a quadrupole mass

filter detected using a conversion dynodeelectron multiplier arrangement and recorded as a

function of their arrival time distributions (ATDs)

In the drift cell the ions experience a constant force from the electric field (E) which is

balance by a retarding frictional force due the collisions with the buffer gas resulting in a

constant drift velocity (vd) The drift velocity is proportional to the electric field and can be

described by equation 13

(1)

S3

where the proportionality constant (K) is the ion mobility The absolute ion mobility is

dependent on the temperature (T) and the pressure (P) of the buffer gas and it is normally

converted to the standard state reduced mobility (K0) by equation 2

(2)

Since the ions that leave the drift cell are mass analyzed and detected as a function of their

arrival time (tA) the reduced mobility can be determined4 from the instrument parameters by

equation 3 and by plotting tA versus PV

(3)

where l is the length of the drift cell (4503 cm) V denotes the voltage across the cell P is the

gas pressure (Torr) and t0 refers to the time the ions spend outside the drift cell before hitting

the detector

The reduced mobility can be related in terms of the collision cross sections (σ) by equation

4 using the kinetic theory of gases3

(4)

where q denotes the ion charge N is the buffer gas number density at STP kb is the

Boltzmann constant and micro refers to the reduced mass of the ionhelium collision

The arrival time distributions can be fitted calculating the flux of ions existing the drift

tube In this context by using the ion transport theory and assuming that the ion packet is

taken as a periodic delta function the flux is given by equation 53 4

S4

(5)

where s is the initial ion density a denotes the area of the exit aperture α is the loss of ions

due to reactions in the drift tube z refers to the distance of the ion traveled r0 is the radius of

the initial ion packet and DL and DT are to the longitudinal and transverse diffusion

coefficients respectively From this equation the arrival time peak shape expected for a pulse

of ions with a single collision cross section can be calculated

As a result ions of different oligomeric states but with the same mz can be separated and

the experimental reduced mobility and the collision cross sections give information

concerning to the three-dimensional configurations of the ions For ions with distinct

conformations of the same oligomer the extended conformers experience more collisions

with the buffer gas than compact ones resulting in larger cross sections and longer arrival

times For oligomers with the same nz where n is the oligomer number and z is the charge

larger oligomers pass through the drift cell faster than small ones since they have a higher

charge per unit cross section hence trimers arrive before dimers that arrive before monomer

at the same nz

S122 Transmission electron microscopy (TEM)

TEM analyses were carried out using a JEOL 123 microscope an ORCA camera and

AMT Image Capture Software v 524

S123 Explicit solvent molecular dynamics and binding simulations

MD Simulations Explicit solvent MD simulations were carried out using the Amber 12

package5 The initial structure of fully extended Aβ1-42 was built using the tleap module and

utilized the Amber 12SB force field The initial structures of folded Aβ1-42 were obtained S5

from the simulations of Sgourakis et al The two most abundant structure families were

utilized The force field of PGG was built following the RESP ESP charge derive protocol

version III6 7 and some parameters were taken from the general Amber force field (GAFF) as

previously described8 The system containing one Aβ1-42 and one PGG was solvated in TIP3P9

water box using a spacing distance of 11 Aring Three additional Na+ ions were added to

neutralize the total charge Several minimization and heating cycles were performed to proper

equilibrate the system The MD simulation was performed in the NPT ensemble (ntp = 1 ntb

= 2) using the periodic boundary condition and a time step of 2 fs Temperature was regulated

by Langevin dynamics (ntt = 3) with a collision frequency of 10 The MD trajectories were

100-ns long for Complexes 1-2 and 200-ns long for Complexes 3-4 Two independent

trajectories were simulated

MM-GBSA The binding energy was evaluated using the molecular mechanics-

generalized Bornsurface area (MM-GBSA) module available in the Amber 12 package5

The solvation energy is represented by the generalized Born term (the polar part of the

solvation) plus a surface area term (the hydrophobic part of the solvation free energy)

S6

S2 Effect of PGG on early Aβ1-40 amyloid aggregation

S21 Mass spectra of Aβ1-40 and PGG mixtures

Figure S1 ESI-Q spectra of Aβ1-40 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-40PGG mixtures

The peaks are noted in brackets where the first number (in black) is the number of Aβ

molecules whereas the second number (in red) represents the number of bound PGG and the

charge is noted as a superscript The Aβ1-40 mass spectrum (Fig A) shows two major peaks at

mz 1081 and 1442 which refer to the Aβ monomers [1]-4 and [1]-3 respectively The minor

peak at mz 1731 correspond to Aβ dimer [2]-5 and tetramer [4]-10 species From the mass

spectrum obtained for the Aβ1-40PGG mixture at 11 molar ratio (Fig B) the most abundant

peaks of Aβ1-40 hetero complexes at mz 1318 and 1552 are attributed to the Aβ monomer with S7

one ([1+1]-4) and two ([1+2]-4) PGG molecules bound respectively The minor peaks at mz

1757 and 1920 refer to the monomer bonded to one PGG molecule ([1+1]-3) and dimer and

tetramer bonded to one and two PGG molecules ([2+1]-5 and [4+2]-10) respectively The

remaining Aβ1-40 homoligomers are the monomers at mz 1081([n]z = [1]-4) and 1442 ([n]z =

[1]-3) At Aβ1-40PGG 110 molar ratio (Fig C) the population of the heteroligomer peaks

increase at mz 1318 1552 1757 and 1920

S8

S22 Arrival Time Distributions (ATD) and Collision Cross Sections (CCS) for Aβ1-40

Figure S2 ATDs of Aβ1-40 (10 microM) The peak at mz 1081 refers to a single Aβ1-40 monomer

with a collision cross section of 750 Aring2 while two different conformations are found for the

peak at mz 1442 (621 Aring2 and 688 Aring2) The mz 1731 ATD displays larger and extended Aβ

oligomers a dimer (1156 Aring2) and a tetramer (2078 Aring2)

S9

Table S1 Collision cross section for homoligomers of Aβ1-40

mz n

Aβ1-40

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

1081 1 -4 750 621

1442 1 -3 621 621

1442 1 -3 688 621

1731 2 -5 1156 986

1731 4 -10 2078 1565

a values in Aring2

b given by σiso(n) = σAβ1-40mon n23

S10

S23 ATD and CCS for Aβ1-40 incubated with PGG

Figure S3 ATDs of Aβ1-40 (10 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 1318 and 1757 refer to Aβ1-40 monomers bound to one PGG molecule with cross

sections of 746 785 724 and 759 Aring2 whereas the mz 1553 ATD displays a compact and an

extended monomers bound to two PGG molecules with cross section of 851 and 901 Aring

respectively Dimer and tetramer complexes with one and two PGG molecules are also

detected at mz 1920 with cross sections of 1087 and 1762 Aring respectively

S11

Table S2 Collision cross section for heteroligomers of Aβ1-40 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-40

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

40ad

σiso(n)

Corrected Aβ1-40

ae

σcorr(nm)

1318 1 1 -4 746 706 1057152 621 656

1318 1 1 -4 785 706 1112419 621 691

1552 1 2 -4 851 786 1083349 621 673

1552 1 2 -4 901 786 1147000 621 712

1757 1 1 -3 724 706 1025976 621 637

1757 1 1 -3 759 706 1075574 621 668

1920 2 1 -5 1087 1054 1031260 986 1017

1920 4 2 -10 1762 1673 1053071 1565 1648

a values in Aring2

b isotropic cross section calculated as σiso(nm) = [n σAβ1-40mon32 + m σPGGmon

32]23 where

n and m are the number of Aβ1-40 and PGG molecules respectively and σAβ1-40mon (621 Aring2)

and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-40 monomer and

12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the collision

cross section of PGG (220 Aring2) was obtained from averaging the cross sections of geometry-

optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-40mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S12

S13

S3 Effect of PGG on early Aβ1-42 amyloid aggregation

S31 Mass spectra of Aβ1-42 and PGG mixtures

Figure S4 ESI-Q spectra of Aβ1-42 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-42PGG mixtures

The Aβ1-42 mass spectrum (Fig A) displays one major peak at mz 1504 which correspond to

the triply charged monomer [1]-3 whereas the minor peaks at mz 1128 and 1805 refer to Aβ

monomers [1]-4 and Aβ dimer tetramer hexamer and dodecamer ([2]-5 [4]-10 [6]-15 and [12]-

30) respectively The mass spectrum obtained for the Aβ1-42PGG mixture at 11 molar ratio

(Fig B) reveals the formation of different Aβ hetero complexes where the peaks at mz 1364

([1+1]-4) 1598 ([1+2]-4) 1818 ([1+1]-3) are attributed to the monomers bounded to one and

two PGG molecules whereas the peak at mz 1994 correspond to the complexes formed by S14

dimer tetramer and hexamer bounded to one two and three PGG molecules ([2+1]-5 ([4+2]-10

and ([6+3]-15) respectively The remaining homoligomer are the monomers at mz 1128

[1]-4 and 1504 [1]-3 At Aβ1-42PGG 110 molar ratio (Fig C) the population increase for the

peaks at mz 1364 1598 1818 and 1994 which correspond to the Aβ1-42PGG complexes

S15

S32 ATD and CCS for Aβ1-42

Figure S5 ATDs of Aβ1-42 (10 microM) The peaks at mz 1128 (785 and 827 Aring2) and 1504 (643

and 696 Aring2) refer to the Aβ1-42 monomers with different conformations whereas the mz 1805

ATD reveals the presence of a dimer (1248 Aring2) a tetramer (2182 Aring2) a hexamer (2891 Aring2)

and a dodecamer (4640 Aring2)

S16

Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 2: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

S1 Materials and Methods

S11 Materials and Sample preparation

Peptide and sample preparation

Full-length Aβ1-40 (DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVV)

and Aβ1-42 (DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA) peptides

were synthesized by N-9-fluorenylmethoxycarnonyl (FMOC) chemistry and further purified

by reverse-phase HPLC Their quality was validated by mass spectrometry and amino acids

analysis as previously described1 The samples were prepared in ammonium acetate buffer

(10 mM pH 74) to the final concentration of 10 μM

Aβ1-11 (DAEFRHDSGYE) and Aβ11-22 (EVHHQKLVFFAE) peptides with free termini

were purchased from GenScrip USA Inc (Piscataway NJ) and their samples prepared in

submicron filtered water (HPLC grade) to the final concentration of 100 microM 12346-penta-

O-galloyl-β-D-glucopyranose (PGG) was purchased from Sigma-Aldrich (St Louis MO

USA) and its sample prepared in water containing 20 (vv) of methanol purchased from

TCI America (Portland OR USA)

Full-length (Aβ1-40 and Aβ1-42) and the Aβ fragments (Aβ1-11 and Aβ11-22) were incubated

with the ligand at 11 and 110 molar ratios and positive controls were performed using the

Aβ solutions without the ligand The Aβ1-40 and Aβ1-42 were incubated without and with PGG

and immediately analyzed by ion mobility spectrometry coupled to mass spectrometry (IMS-

MS) whereas IMS-MS analyses of the Aβ1-11 and Aβ11-22 peptides were performed after 1

week of incubation time Additionally the samples were analyzed by transmission electron

microscopy (TEM) after 2 days and 1 week of incubation time at room temperature for the

full-length and Aβ fragments respectively In this context the samples were adsorbed onto

300 mesh formvarcarbon copper grids (Electron Microscopy Sciences) and after 15 min

excess samples was removed and grids were stained for 1 min with 2 uranyl acetate S2

Additionally Aβ1-42 were incubated for 3 days at room temperature and then PGG was

added at Aβ1-42PGG molar ratios of 11 and 110 After more 2 days of incubation the

mixtures followed to TEM analysis

S12 Methods

S121 Ion mobility spectrometry coupled mass spectrometry (IMS-MS)

Samples were analyzed on a home-built ion mobility spectrometer coupled to a mass

spectrometer composed by a nano-electrospray ionization (nano-ESI) source an ion funnel a

temperature-controlled drift cell and a quadrupole mass filter followed by an electron

multiplier detector2 Briefly the ions were continuously generated by a nano-ESI source

focused and stored in the ion funnel A pulse (10 micros) of ions was injected into a drift cell

filled with 3-5 Torr of helium gas (buffer gas) where they gently passed through under the

influence of a weak electric field Normally the injection energy was kept as ~40 eV to

minimize thermal heating of the ions during the injection process but it can be varied from

~20 to ~150 eV The ions exiting the drift cell were mass analyzed by a quadrupole mass

filter detected using a conversion dynodeelectron multiplier arrangement and recorded as a

function of their arrival time distributions (ATDs)

In the drift cell the ions experience a constant force from the electric field (E) which is

balance by a retarding frictional force due the collisions with the buffer gas resulting in a

constant drift velocity (vd) The drift velocity is proportional to the electric field and can be

described by equation 13

(1)

S3

where the proportionality constant (K) is the ion mobility The absolute ion mobility is

dependent on the temperature (T) and the pressure (P) of the buffer gas and it is normally

converted to the standard state reduced mobility (K0) by equation 2

(2)

Since the ions that leave the drift cell are mass analyzed and detected as a function of their

arrival time (tA) the reduced mobility can be determined4 from the instrument parameters by

equation 3 and by plotting tA versus PV

(3)

where l is the length of the drift cell (4503 cm) V denotes the voltage across the cell P is the

gas pressure (Torr) and t0 refers to the time the ions spend outside the drift cell before hitting

the detector

The reduced mobility can be related in terms of the collision cross sections (σ) by equation

4 using the kinetic theory of gases3

(4)

where q denotes the ion charge N is the buffer gas number density at STP kb is the

Boltzmann constant and micro refers to the reduced mass of the ionhelium collision

The arrival time distributions can be fitted calculating the flux of ions existing the drift

tube In this context by using the ion transport theory and assuming that the ion packet is

taken as a periodic delta function the flux is given by equation 53 4

S4

(5)

where s is the initial ion density a denotes the area of the exit aperture α is the loss of ions

due to reactions in the drift tube z refers to the distance of the ion traveled r0 is the radius of

the initial ion packet and DL and DT are to the longitudinal and transverse diffusion

coefficients respectively From this equation the arrival time peak shape expected for a pulse

of ions with a single collision cross section can be calculated

As a result ions of different oligomeric states but with the same mz can be separated and

the experimental reduced mobility and the collision cross sections give information

concerning to the three-dimensional configurations of the ions For ions with distinct

conformations of the same oligomer the extended conformers experience more collisions

with the buffer gas than compact ones resulting in larger cross sections and longer arrival

times For oligomers with the same nz where n is the oligomer number and z is the charge

larger oligomers pass through the drift cell faster than small ones since they have a higher

charge per unit cross section hence trimers arrive before dimers that arrive before monomer

at the same nz

S122 Transmission electron microscopy (TEM)

TEM analyses were carried out using a JEOL 123 microscope an ORCA camera and

AMT Image Capture Software v 524

S123 Explicit solvent molecular dynamics and binding simulations

MD Simulations Explicit solvent MD simulations were carried out using the Amber 12

package5 The initial structure of fully extended Aβ1-42 was built using the tleap module and

utilized the Amber 12SB force field The initial structures of folded Aβ1-42 were obtained S5

from the simulations of Sgourakis et al The two most abundant structure families were

utilized The force field of PGG was built following the RESP ESP charge derive protocol

version III6 7 and some parameters were taken from the general Amber force field (GAFF) as

previously described8 The system containing one Aβ1-42 and one PGG was solvated in TIP3P9

water box using a spacing distance of 11 Aring Three additional Na+ ions were added to

neutralize the total charge Several minimization and heating cycles were performed to proper

equilibrate the system The MD simulation was performed in the NPT ensemble (ntp = 1 ntb

= 2) using the periodic boundary condition and a time step of 2 fs Temperature was regulated

by Langevin dynamics (ntt = 3) with a collision frequency of 10 The MD trajectories were

100-ns long for Complexes 1-2 and 200-ns long for Complexes 3-4 Two independent

trajectories were simulated

MM-GBSA The binding energy was evaluated using the molecular mechanics-

generalized Bornsurface area (MM-GBSA) module available in the Amber 12 package5

The solvation energy is represented by the generalized Born term (the polar part of the

solvation) plus a surface area term (the hydrophobic part of the solvation free energy)

S6

S2 Effect of PGG on early Aβ1-40 amyloid aggregation

S21 Mass spectra of Aβ1-40 and PGG mixtures

Figure S1 ESI-Q spectra of Aβ1-40 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-40PGG mixtures

The peaks are noted in brackets where the first number (in black) is the number of Aβ

molecules whereas the second number (in red) represents the number of bound PGG and the

charge is noted as a superscript The Aβ1-40 mass spectrum (Fig A) shows two major peaks at

mz 1081 and 1442 which refer to the Aβ monomers [1]-4 and [1]-3 respectively The minor

peak at mz 1731 correspond to Aβ dimer [2]-5 and tetramer [4]-10 species From the mass

spectrum obtained for the Aβ1-40PGG mixture at 11 molar ratio (Fig B) the most abundant

peaks of Aβ1-40 hetero complexes at mz 1318 and 1552 are attributed to the Aβ monomer with S7

one ([1+1]-4) and two ([1+2]-4) PGG molecules bound respectively The minor peaks at mz

1757 and 1920 refer to the monomer bonded to one PGG molecule ([1+1]-3) and dimer and

tetramer bonded to one and two PGG molecules ([2+1]-5 and [4+2]-10) respectively The

remaining Aβ1-40 homoligomers are the monomers at mz 1081([n]z = [1]-4) and 1442 ([n]z =

[1]-3) At Aβ1-40PGG 110 molar ratio (Fig C) the population of the heteroligomer peaks

increase at mz 1318 1552 1757 and 1920

S8

S22 Arrival Time Distributions (ATD) and Collision Cross Sections (CCS) for Aβ1-40

Figure S2 ATDs of Aβ1-40 (10 microM) The peak at mz 1081 refers to a single Aβ1-40 monomer

with a collision cross section of 750 Aring2 while two different conformations are found for the

peak at mz 1442 (621 Aring2 and 688 Aring2) The mz 1731 ATD displays larger and extended Aβ

oligomers a dimer (1156 Aring2) and a tetramer (2078 Aring2)

S9

Table S1 Collision cross section for homoligomers of Aβ1-40

mz n

Aβ1-40

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

1081 1 -4 750 621

1442 1 -3 621 621

1442 1 -3 688 621

1731 2 -5 1156 986

1731 4 -10 2078 1565

a values in Aring2

b given by σiso(n) = σAβ1-40mon n23

S10

S23 ATD and CCS for Aβ1-40 incubated with PGG

Figure S3 ATDs of Aβ1-40 (10 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 1318 and 1757 refer to Aβ1-40 monomers bound to one PGG molecule with cross

sections of 746 785 724 and 759 Aring2 whereas the mz 1553 ATD displays a compact and an

extended monomers bound to two PGG molecules with cross section of 851 and 901 Aring

respectively Dimer and tetramer complexes with one and two PGG molecules are also

detected at mz 1920 with cross sections of 1087 and 1762 Aring respectively

S11

Table S2 Collision cross section for heteroligomers of Aβ1-40 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-40

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

40ad

σiso(n)

Corrected Aβ1-40

ae

σcorr(nm)

1318 1 1 -4 746 706 1057152 621 656

1318 1 1 -4 785 706 1112419 621 691

1552 1 2 -4 851 786 1083349 621 673

1552 1 2 -4 901 786 1147000 621 712

1757 1 1 -3 724 706 1025976 621 637

1757 1 1 -3 759 706 1075574 621 668

1920 2 1 -5 1087 1054 1031260 986 1017

1920 4 2 -10 1762 1673 1053071 1565 1648

a values in Aring2

b isotropic cross section calculated as σiso(nm) = [n σAβ1-40mon32 + m σPGGmon

32]23 where

n and m are the number of Aβ1-40 and PGG molecules respectively and σAβ1-40mon (621 Aring2)

and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-40 monomer and

12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the collision

cross section of PGG (220 Aring2) was obtained from averaging the cross sections of geometry-

optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-40mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S12

S13

S3 Effect of PGG on early Aβ1-42 amyloid aggregation

S31 Mass spectra of Aβ1-42 and PGG mixtures

Figure S4 ESI-Q spectra of Aβ1-42 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-42PGG mixtures

The Aβ1-42 mass spectrum (Fig A) displays one major peak at mz 1504 which correspond to

the triply charged monomer [1]-3 whereas the minor peaks at mz 1128 and 1805 refer to Aβ

monomers [1]-4 and Aβ dimer tetramer hexamer and dodecamer ([2]-5 [4]-10 [6]-15 and [12]-

30) respectively The mass spectrum obtained for the Aβ1-42PGG mixture at 11 molar ratio

(Fig B) reveals the formation of different Aβ hetero complexes where the peaks at mz 1364

([1+1]-4) 1598 ([1+2]-4) 1818 ([1+1]-3) are attributed to the monomers bounded to one and

two PGG molecules whereas the peak at mz 1994 correspond to the complexes formed by S14

dimer tetramer and hexamer bounded to one two and three PGG molecules ([2+1]-5 ([4+2]-10

and ([6+3]-15) respectively The remaining homoligomer are the monomers at mz 1128

[1]-4 and 1504 [1]-3 At Aβ1-42PGG 110 molar ratio (Fig C) the population increase for the

peaks at mz 1364 1598 1818 and 1994 which correspond to the Aβ1-42PGG complexes

S15

S32 ATD and CCS for Aβ1-42

Figure S5 ATDs of Aβ1-42 (10 microM) The peaks at mz 1128 (785 and 827 Aring2) and 1504 (643

and 696 Aring2) refer to the Aβ1-42 monomers with different conformations whereas the mz 1805

ATD reveals the presence of a dimer (1248 Aring2) a tetramer (2182 Aring2) a hexamer (2891 Aring2)

and a dodecamer (4640 Aring2)

S16

Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 3: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

Additionally Aβ1-42 were incubated for 3 days at room temperature and then PGG was

added at Aβ1-42PGG molar ratios of 11 and 110 After more 2 days of incubation the

mixtures followed to TEM analysis

S12 Methods

S121 Ion mobility spectrometry coupled mass spectrometry (IMS-MS)

Samples were analyzed on a home-built ion mobility spectrometer coupled to a mass

spectrometer composed by a nano-electrospray ionization (nano-ESI) source an ion funnel a

temperature-controlled drift cell and a quadrupole mass filter followed by an electron

multiplier detector2 Briefly the ions were continuously generated by a nano-ESI source

focused and stored in the ion funnel A pulse (10 micros) of ions was injected into a drift cell

filled with 3-5 Torr of helium gas (buffer gas) where they gently passed through under the

influence of a weak electric field Normally the injection energy was kept as ~40 eV to

minimize thermal heating of the ions during the injection process but it can be varied from

~20 to ~150 eV The ions exiting the drift cell were mass analyzed by a quadrupole mass

filter detected using a conversion dynodeelectron multiplier arrangement and recorded as a

function of their arrival time distributions (ATDs)

In the drift cell the ions experience a constant force from the electric field (E) which is

balance by a retarding frictional force due the collisions with the buffer gas resulting in a

constant drift velocity (vd) The drift velocity is proportional to the electric field and can be

described by equation 13

(1)

S3

where the proportionality constant (K) is the ion mobility The absolute ion mobility is

dependent on the temperature (T) and the pressure (P) of the buffer gas and it is normally

converted to the standard state reduced mobility (K0) by equation 2

(2)

Since the ions that leave the drift cell are mass analyzed and detected as a function of their

arrival time (tA) the reduced mobility can be determined4 from the instrument parameters by

equation 3 and by plotting tA versus PV

(3)

where l is the length of the drift cell (4503 cm) V denotes the voltage across the cell P is the

gas pressure (Torr) and t0 refers to the time the ions spend outside the drift cell before hitting

the detector

The reduced mobility can be related in terms of the collision cross sections (σ) by equation

4 using the kinetic theory of gases3

(4)

where q denotes the ion charge N is the buffer gas number density at STP kb is the

Boltzmann constant and micro refers to the reduced mass of the ionhelium collision

The arrival time distributions can be fitted calculating the flux of ions existing the drift

tube In this context by using the ion transport theory and assuming that the ion packet is

taken as a periodic delta function the flux is given by equation 53 4

S4

(5)

where s is the initial ion density a denotes the area of the exit aperture α is the loss of ions

due to reactions in the drift tube z refers to the distance of the ion traveled r0 is the radius of

the initial ion packet and DL and DT are to the longitudinal and transverse diffusion

coefficients respectively From this equation the arrival time peak shape expected for a pulse

of ions with a single collision cross section can be calculated

As a result ions of different oligomeric states but with the same mz can be separated and

the experimental reduced mobility and the collision cross sections give information

concerning to the three-dimensional configurations of the ions For ions with distinct

conformations of the same oligomer the extended conformers experience more collisions

with the buffer gas than compact ones resulting in larger cross sections and longer arrival

times For oligomers with the same nz where n is the oligomer number and z is the charge

larger oligomers pass through the drift cell faster than small ones since they have a higher

charge per unit cross section hence trimers arrive before dimers that arrive before monomer

at the same nz

S122 Transmission electron microscopy (TEM)

TEM analyses were carried out using a JEOL 123 microscope an ORCA camera and

AMT Image Capture Software v 524

S123 Explicit solvent molecular dynamics and binding simulations

MD Simulations Explicit solvent MD simulations were carried out using the Amber 12

package5 The initial structure of fully extended Aβ1-42 was built using the tleap module and

utilized the Amber 12SB force field The initial structures of folded Aβ1-42 were obtained S5

from the simulations of Sgourakis et al The two most abundant structure families were

utilized The force field of PGG was built following the RESP ESP charge derive protocol

version III6 7 and some parameters were taken from the general Amber force field (GAFF) as

previously described8 The system containing one Aβ1-42 and one PGG was solvated in TIP3P9

water box using a spacing distance of 11 Aring Three additional Na+ ions were added to

neutralize the total charge Several minimization and heating cycles were performed to proper

equilibrate the system The MD simulation was performed in the NPT ensemble (ntp = 1 ntb

= 2) using the periodic boundary condition and a time step of 2 fs Temperature was regulated

by Langevin dynamics (ntt = 3) with a collision frequency of 10 The MD trajectories were

100-ns long for Complexes 1-2 and 200-ns long for Complexes 3-4 Two independent

trajectories were simulated

MM-GBSA The binding energy was evaluated using the molecular mechanics-

generalized Bornsurface area (MM-GBSA) module available in the Amber 12 package5

The solvation energy is represented by the generalized Born term (the polar part of the

solvation) plus a surface area term (the hydrophobic part of the solvation free energy)

S6

S2 Effect of PGG on early Aβ1-40 amyloid aggregation

S21 Mass spectra of Aβ1-40 and PGG mixtures

Figure S1 ESI-Q spectra of Aβ1-40 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-40PGG mixtures

The peaks are noted in brackets where the first number (in black) is the number of Aβ

molecules whereas the second number (in red) represents the number of bound PGG and the

charge is noted as a superscript The Aβ1-40 mass spectrum (Fig A) shows two major peaks at

mz 1081 and 1442 which refer to the Aβ monomers [1]-4 and [1]-3 respectively The minor

peak at mz 1731 correspond to Aβ dimer [2]-5 and tetramer [4]-10 species From the mass

spectrum obtained for the Aβ1-40PGG mixture at 11 molar ratio (Fig B) the most abundant

peaks of Aβ1-40 hetero complexes at mz 1318 and 1552 are attributed to the Aβ monomer with S7

one ([1+1]-4) and two ([1+2]-4) PGG molecules bound respectively The minor peaks at mz

1757 and 1920 refer to the monomer bonded to one PGG molecule ([1+1]-3) and dimer and

tetramer bonded to one and two PGG molecules ([2+1]-5 and [4+2]-10) respectively The

remaining Aβ1-40 homoligomers are the monomers at mz 1081([n]z = [1]-4) and 1442 ([n]z =

[1]-3) At Aβ1-40PGG 110 molar ratio (Fig C) the population of the heteroligomer peaks

increase at mz 1318 1552 1757 and 1920

S8

S22 Arrival Time Distributions (ATD) and Collision Cross Sections (CCS) for Aβ1-40

Figure S2 ATDs of Aβ1-40 (10 microM) The peak at mz 1081 refers to a single Aβ1-40 monomer

with a collision cross section of 750 Aring2 while two different conformations are found for the

peak at mz 1442 (621 Aring2 and 688 Aring2) The mz 1731 ATD displays larger and extended Aβ

oligomers a dimer (1156 Aring2) and a tetramer (2078 Aring2)

S9

Table S1 Collision cross section for homoligomers of Aβ1-40

mz n

Aβ1-40

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

1081 1 -4 750 621

1442 1 -3 621 621

1442 1 -3 688 621

1731 2 -5 1156 986

1731 4 -10 2078 1565

a values in Aring2

b given by σiso(n) = σAβ1-40mon n23

S10

S23 ATD and CCS for Aβ1-40 incubated with PGG

Figure S3 ATDs of Aβ1-40 (10 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 1318 and 1757 refer to Aβ1-40 monomers bound to one PGG molecule with cross

sections of 746 785 724 and 759 Aring2 whereas the mz 1553 ATD displays a compact and an

extended monomers bound to two PGG molecules with cross section of 851 and 901 Aring

respectively Dimer and tetramer complexes with one and two PGG molecules are also

detected at mz 1920 with cross sections of 1087 and 1762 Aring respectively

S11

Table S2 Collision cross section for heteroligomers of Aβ1-40 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-40

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

40ad

σiso(n)

Corrected Aβ1-40

ae

σcorr(nm)

1318 1 1 -4 746 706 1057152 621 656

1318 1 1 -4 785 706 1112419 621 691

1552 1 2 -4 851 786 1083349 621 673

1552 1 2 -4 901 786 1147000 621 712

1757 1 1 -3 724 706 1025976 621 637

1757 1 1 -3 759 706 1075574 621 668

1920 2 1 -5 1087 1054 1031260 986 1017

1920 4 2 -10 1762 1673 1053071 1565 1648

a values in Aring2

b isotropic cross section calculated as σiso(nm) = [n σAβ1-40mon32 + m σPGGmon

32]23 where

n and m are the number of Aβ1-40 and PGG molecules respectively and σAβ1-40mon (621 Aring2)

and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-40 monomer and

12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the collision

cross section of PGG (220 Aring2) was obtained from averaging the cross sections of geometry-

optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-40mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S12

S13

S3 Effect of PGG on early Aβ1-42 amyloid aggregation

S31 Mass spectra of Aβ1-42 and PGG mixtures

Figure S4 ESI-Q spectra of Aβ1-42 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-42PGG mixtures

The Aβ1-42 mass spectrum (Fig A) displays one major peak at mz 1504 which correspond to

the triply charged monomer [1]-3 whereas the minor peaks at mz 1128 and 1805 refer to Aβ

monomers [1]-4 and Aβ dimer tetramer hexamer and dodecamer ([2]-5 [4]-10 [6]-15 and [12]-

30) respectively The mass spectrum obtained for the Aβ1-42PGG mixture at 11 molar ratio

(Fig B) reveals the formation of different Aβ hetero complexes where the peaks at mz 1364

([1+1]-4) 1598 ([1+2]-4) 1818 ([1+1]-3) are attributed to the monomers bounded to one and

two PGG molecules whereas the peak at mz 1994 correspond to the complexes formed by S14

dimer tetramer and hexamer bounded to one two and three PGG molecules ([2+1]-5 ([4+2]-10

and ([6+3]-15) respectively The remaining homoligomer are the monomers at mz 1128

[1]-4 and 1504 [1]-3 At Aβ1-42PGG 110 molar ratio (Fig C) the population increase for the

peaks at mz 1364 1598 1818 and 1994 which correspond to the Aβ1-42PGG complexes

S15

S32 ATD and CCS for Aβ1-42

Figure S5 ATDs of Aβ1-42 (10 microM) The peaks at mz 1128 (785 and 827 Aring2) and 1504 (643

and 696 Aring2) refer to the Aβ1-42 monomers with different conformations whereas the mz 1805

ATD reveals the presence of a dimer (1248 Aring2) a tetramer (2182 Aring2) a hexamer (2891 Aring2)

and a dodecamer (4640 Aring2)

S16

Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 4: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

where the proportionality constant (K) is the ion mobility The absolute ion mobility is

dependent on the temperature (T) and the pressure (P) of the buffer gas and it is normally

converted to the standard state reduced mobility (K0) by equation 2

(2)

Since the ions that leave the drift cell are mass analyzed and detected as a function of their

arrival time (tA) the reduced mobility can be determined4 from the instrument parameters by

equation 3 and by plotting tA versus PV

(3)

where l is the length of the drift cell (4503 cm) V denotes the voltage across the cell P is the

gas pressure (Torr) and t0 refers to the time the ions spend outside the drift cell before hitting

the detector

The reduced mobility can be related in terms of the collision cross sections (σ) by equation

4 using the kinetic theory of gases3

(4)

where q denotes the ion charge N is the buffer gas number density at STP kb is the

Boltzmann constant and micro refers to the reduced mass of the ionhelium collision

The arrival time distributions can be fitted calculating the flux of ions existing the drift

tube In this context by using the ion transport theory and assuming that the ion packet is

taken as a periodic delta function the flux is given by equation 53 4

S4

(5)

where s is the initial ion density a denotes the area of the exit aperture α is the loss of ions

due to reactions in the drift tube z refers to the distance of the ion traveled r0 is the radius of

the initial ion packet and DL and DT are to the longitudinal and transverse diffusion

coefficients respectively From this equation the arrival time peak shape expected for a pulse

of ions with a single collision cross section can be calculated

As a result ions of different oligomeric states but with the same mz can be separated and

the experimental reduced mobility and the collision cross sections give information

concerning to the three-dimensional configurations of the ions For ions with distinct

conformations of the same oligomer the extended conformers experience more collisions

with the buffer gas than compact ones resulting in larger cross sections and longer arrival

times For oligomers with the same nz where n is the oligomer number and z is the charge

larger oligomers pass through the drift cell faster than small ones since they have a higher

charge per unit cross section hence trimers arrive before dimers that arrive before monomer

at the same nz

S122 Transmission electron microscopy (TEM)

TEM analyses were carried out using a JEOL 123 microscope an ORCA camera and

AMT Image Capture Software v 524

S123 Explicit solvent molecular dynamics and binding simulations

MD Simulations Explicit solvent MD simulations were carried out using the Amber 12

package5 The initial structure of fully extended Aβ1-42 was built using the tleap module and

utilized the Amber 12SB force field The initial structures of folded Aβ1-42 were obtained S5

from the simulations of Sgourakis et al The two most abundant structure families were

utilized The force field of PGG was built following the RESP ESP charge derive protocol

version III6 7 and some parameters were taken from the general Amber force field (GAFF) as

previously described8 The system containing one Aβ1-42 and one PGG was solvated in TIP3P9

water box using a spacing distance of 11 Aring Three additional Na+ ions were added to

neutralize the total charge Several minimization and heating cycles were performed to proper

equilibrate the system The MD simulation was performed in the NPT ensemble (ntp = 1 ntb

= 2) using the periodic boundary condition and a time step of 2 fs Temperature was regulated

by Langevin dynamics (ntt = 3) with a collision frequency of 10 The MD trajectories were

100-ns long for Complexes 1-2 and 200-ns long for Complexes 3-4 Two independent

trajectories were simulated

MM-GBSA The binding energy was evaluated using the molecular mechanics-

generalized Bornsurface area (MM-GBSA) module available in the Amber 12 package5

The solvation energy is represented by the generalized Born term (the polar part of the

solvation) plus a surface area term (the hydrophobic part of the solvation free energy)

S6

S2 Effect of PGG on early Aβ1-40 amyloid aggregation

S21 Mass spectra of Aβ1-40 and PGG mixtures

Figure S1 ESI-Q spectra of Aβ1-40 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-40PGG mixtures

The peaks are noted in brackets where the first number (in black) is the number of Aβ

molecules whereas the second number (in red) represents the number of bound PGG and the

charge is noted as a superscript The Aβ1-40 mass spectrum (Fig A) shows two major peaks at

mz 1081 and 1442 which refer to the Aβ monomers [1]-4 and [1]-3 respectively The minor

peak at mz 1731 correspond to Aβ dimer [2]-5 and tetramer [4]-10 species From the mass

spectrum obtained for the Aβ1-40PGG mixture at 11 molar ratio (Fig B) the most abundant

peaks of Aβ1-40 hetero complexes at mz 1318 and 1552 are attributed to the Aβ monomer with S7

one ([1+1]-4) and two ([1+2]-4) PGG molecules bound respectively The minor peaks at mz

1757 and 1920 refer to the monomer bonded to one PGG molecule ([1+1]-3) and dimer and

tetramer bonded to one and two PGG molecules ([2+1]-5 and [4+2]-10) respectively The

remaining Aβ1-40 homoligomers are the monomers at mz 1081([n]z = [1]-4) and 1442 ([n]z =

[1]-3) At Aβ1-40PGG 110 molar ratio (Fig C) the population of the heteroligomer peaks

increase at mz 1318 1552 1757 and 1920

S8

S22 Arrival Time Distributions (ATD) and Collision Cross Sections (CCS) for Aβ1-40

Figure S2 ATDs of Aβ1-40 (10 microM) The peak at mz 1081 refers to a single Aβ1-40 monomer

with a collision cross section of 750 Aring2 while two different conformations are found for the

peak at mz 1442 (621 Aring2 and 688 Aring2) The mz 1731 ATD displays larger and extended Aβ

oligomers a dimer (1156 Aring2) and a tetramer (2078 Aring2)

S9

Table S1 Collision cross section for homoligomers of Aβ1-40

mz n

Aβ1-40

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

1081 1 -4 750 621

1442 1 -3 621 621

1442 1 -3 688 621

1731 2 -5 1156 986

1731 4 -10 2078 1565

a values in Aring2

b given by σiso(n) = σAβ1-40mon n23

S10

S23 ATD and CCS for Aβ1-40 incubated with PGG

Figure S3 ATDs of Aβ1-40 (10 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 1318 and 1757 refer to Aβ1-40 monomers bound to one PGG molecule with cross

sections of 746 785 724 and 759 Aring2 whereas the mz 1553 ATD displays a compact and an

extended monomers bound to two PGG molecules with cross section of 851 and 901 Aring

respectively Dimer and tetramer complexes with one and two PGG molecules are also

detected at mz 1920 with cross sections of 1087 and 1762 Aring respectively

S11

Table S2 Collision cross section for heteroligomers of Aβ1-40 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-40

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

40ad

σiso(n)

Corrected Aβ1-40

ae

σcorr(nm)

1318 1 1 -4 746 706 1057152 621 656

1318 1 1 -4 785 706 1112419 621 691

1552 1 2 -4 851 786 1083349 621 673

1552 1 2 -4 901 786 1147000 621 712

1757 1 1 -3 724 706 1025976 621 637

1757 1 1 -3 759 706 1075574 621 668

1920 2 1 -5 1087 1054 1031260 986 1017

1920 4 2 -10 1762 1673 1053071 1565 1648

a values in Aring2

b isotropic cross section calculated as σiso(nm) = [n σAβ1-40mon32 + m σPGGmon

32]23 where

n and m are the number of Aβ1-40 and PGG molecules respectively and σAβ1-40mon (621 Aring2)

and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-40 monomer and

12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the collision

cross section of PGG (220 Aring2) was obtained from averaging the cross sections of geometry-

optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-40mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S12

S13

S3 Effect of PGG on early Aβ1-42 amyloid aggregation

S31 Mass spectra of Aβ1-42 and PGG mixtures

Figure S4 ESI-Q spectra of Aβ1-42 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-42PGG mixtures

The Aβ1-42 mass spectrum (Fig A) displays one major peak at mz 1504 which correspond to

the triply charged monomer [1]-3 whereas the minor peaks at mz 1128 and 1805 refer to Aβ

monomers [1]-4 and Aβ dimer tetramer hexamer and dodecamer ([2]-5 [4]-10 [6]-15 and [12]-

30) respectively The mass spectrum obtained for the Aβ1-42PGG mixture at 11 molar ratio

(Fig B) reveals the formation of different Aβ hetero complexes where the peaks at mz 1364

([1+1]-4) 1598 ([1+2]-4) 1818 ([1+1]-3) are attributed to the monomers bounded to one and

two PGG molecules whereas the peak at mz 1994 correspond to the complexes formed by S14

dimer tetramer and hexamer bounded to one two and three PGG molecules ([2+1]-5 ([4+2]-10

and ([6+3]-15) respectively The remaining homoligomer are the monomers at mz 1128

[1]-4 and 1504 [1]-3 At Aβ1-42PGG 110 molar ratio (Fig C) the population increase for the

peaks at mz 1364 1598 1818 and 1994 which correspond to the Aβ1-42PGG complexes

S15

S32 ATD and CCS for Aβ1-42

Figure S5 ATDs of Aβ1-42 (10 microM) The peaks at mz 1128 (785 and 827 Aring2) and 1504 (643

and 696 Aring2) refer to the Aβ1-42 monomers with different conformations whereas the mz 1805

ATD reveals the presence of a dimer (1248 Aring2) a tetramer (2182 Aring2) a hexamer (2891 Aring2)

and a dodecamer (4640 Aring2)

S16

Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 5: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

(5)

where s is the initial ion density a denotes the area of the exit aperture α is the loss of ions

due to reactions in the drift tube z refers to the distance of the ion traveled r0 is the radius of

the initial ion packet and DL and DT are to the longitudinal and transverse diffusion

coefficients respectively From this equation the arrival time peak shape expected for a pulse

of ions with a single collision cross section can be calculated

As a result ions of different oligomeric states but with the same mz can be separated and

the experimental reduced mobility and the collision cross sections give information

concerning to the three-dimensional configurations of the ions For ions with distinct

conformations of the same oligomer the extended conformers experience more collisions

with the buffer gas than compact ones resulting in larger cross sections and longer arrival

times For oligomers with the same nz where n is the oligomer number and z is the charge

larger oligomers pass through the drift cell faster than small ones since they have a higher

charge per unit cross section hence trimers arrive before dimers that arrive before monomer

at the same nz

S122 Transmission electron microscopy (TEM)

TEM analyses were carried out using a JEOL 123 microscope an ORCA camera and

AMT Image Capture Software v 524

S123 Explicit solvent molecular dynamics and binding simulations

MD Simulations Explicit solvent MD simulations were carried out using the Amber 12

package5 The initial structure of fully extended Aβ1-42 was built using the tleap module and

utilized the Amber 12SB force field The initial structures of folded Aβ1-42 were obtained S5

from the simulations of Sgourakis et al The two most abundant structure families were

utilized The force field of PGG was built following the RESP ESP charge derive protocol

version III6 7 and some parameters were taken from the general Amber force field (GAFF) as

previously described8 The system containing one Aβ1-42 and one PGG was solvated in TIP3P9

water box using a spacing distance of 11 Aring Three additional Na+ ions were added to

neutralize the total charge Several minimization and heating cycles were performed to proper

equilibrate the system The MD simulation was performed in the NPT ensemble (ntp = 1 ntb

= 2) using the periodic boundary condition and a time step of 2 fs Temperature was regulated

by Langevin dynamics (ntt = 3) with a collision frequency of 10 The MD trajectories were

100-ns long for Complexes 1-2 and 200-ns long for Complexes 3-4 Two independent

trajectories were simulated

MM-GBSA The binding energy was evaluated using the molecular mechanics-

generalized Bornsurface area (MM-GBSA) module available in the Amber 12 package5

The solvation energy is represented by the generalized Born term (the polar part of the

solvation) plus a surface area term (the hydrophobic part of the solvation free energy)

S6

S2 Effect of PGG on early Aβ1-40 amyloid aggregation

S21 Mass spectra of Aβ1-40 and PGG mixtures

Figure S1 ESI-Q spectra of Aβ1-40 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-40PGG mixtures

The peaks are noted in brackets where the first number (in black) is the number of Aβ

molecules whereas the second number (in red) represents the number of bound PGG and the

charge is noted as a superscript The Aβ1-40 mass spectrum (Fig A) shows two major peaks at

mz 1081 and 1442 which refer to the Aβ monomers [1]-4 and [1]-3 respectively The minor

peak at mz 1731 correspond to Aβ dimer [2]-5 and tetramer [4]-10 species From the mass

spectrum obtained for the Aβ1-40PGG mixture at 11 molar ratio (Fig B) the most abundant

peaks of Aβ1-40 hetero complexes at mz 1318 and 1552 are attributed to the Aβ monomer with S7

one ([1+1]-4) and two ([1+2]-4) PGG molecules bound respectively The minor peaks at mz

1757 and 1920 refer to the monomer bonded to one PGG molecule ([1+1]-3) and dimer and

tetramer bonded to one and two PGG molecules ([2+1]-5 and [4+2]-10) respectively The

remaining Aβ1-40 homoligomers are the monomers at mz 1081([n]z = [1]-4) and 1442 ([n]z =

[1]-3) At Aβ1-40PGG 110 molar ratio (Fig C) the population of the heteroligomer peaks

increase at mz 1318 1552 1757 and 1920

S8

S22 Arrival Time Distributions (ATD) and Collision Cross Sections (CCS) for Aβ1-40

Figure S2 ATDs of Aβ1-40 (10 microM) The peak at mz 1081 refers to a single Aβ1-40 monomer

with a collision cross section of 750 Aring2 while two different conformations are found for the

peak at mz 1442 (621 Aring2 and 688 Aring2) The mz 1731 ATD displays larger and extended Aβ

oligomers a dimer (1156 Aring2) and a tetramer (2078 Aring2)

S9

Table S1 Collision cross section for homoligomers of Aβ1-40

mz n

Aβ1-40

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

1081 1 -4 750 621

1442 1 -3 621 621

1442 1 -3 688 621

1731 2 -5 1156 986

1731 4 -10 2078 1565

a values in Aring2

b given by σiso(n) = σAβ1-40mon n23

S10

S23 ATD and CCS for Aβ1-40 incubated with PGG

Figure S3 ATDs of Aβ1-40 (10 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 1318 and 1757 refer to Aβ1-40 monomers bound to one PGG molecule with cross

sections of 746 785 724 and 759 Aring2 whereas the mz 1553 ATD displays a compact and an

extended monomers bound to two PGG molecules with cross section of 851 and 901 Aring

respectively Dimer and tetramer complexes with one and two PGG molecules are also

detected at mz 1920 with cross sections of 1087 and 1762 Aring respectively

S11

Table S2 Collision cross section for heteroligomers of Aβ1-40 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-40

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

40ad

σiso(n)

Corrected Aβ1-40

ae

σcorr(nm)

1318 1 1 -4 746 706 1057152 621 656

1318 1 1 -4 785 706 1112419 621 691

1552 1 2 -4 851 786 1083349 621 673

1552 1 2 -4 901 786 1147000 621 712

1757 1 1 -3 724 706 1025976 621 637

1757 1 1 -3 759 706 1075574 621 668

1920 2 1 -5 1087 1054 1031260 986 1017

1920 4 2 -10 1762 1673 1053071 1565 1648

a values in Aring2

b isotropic cross section calculated as σiso(nm) = [n σAβ1-40mon32 + m σPGGmon

32]23 where

n and m are the number of Aβ1-40 and PGG molecules respectively and σAβ1-40mon (621 Aring2)

and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-40 monomer and

12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the collision

cross section of PGG (220 Aring2) was obtained from averaging the cross sections of geometry-

optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-40mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S12

S13

S3 Effect of PGG on early Aβ1-42 amyloid aggregation

S31 Mass spectra of Aβ1-42 and PGG mixtures

Figure S4 ESI-Q spectra of Aβ1-42 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-42PGG mixtures

The Aβ1-42 mass spectrum (Fig A) displays one major peak at mz 1504 which correspond to

the triply charged monomer [1]-3 whereas the minor peaks at mz 1128 and 1805 refer to Aβ

monomers [1]-4 and Aβ dimer tetramer hexamer and dodecamer ([2]-5 [4]-10 [6]-15 and [12]-

30) respectively The mass spectrum obtained for the Aβ1-42PGG mixture at 11 molar ratio

(Fig B) reveals the formation of different Aβ hetero complexes where the peaks at mz 1364

([1+1]-4) 1598 ([1+2]-4) 1818 ([1+1]-3) are attributed to the monomers bounded to one and

two PGG molecules whereas the peak at mz 1994 correspond to the complexes formed by S14

dimer tetramer and hexamer bounded to one two and three PGG molecules ([2+1]-5 ([4+2]-10

and ([6+3]-15) respectively The remaining homoligomer are the monomers at mz 1128

[1]-4 and 1504 [1]-3 At Aβ1-42PGG 110 molar ratio (Fig C) the population increase for the

peaks at mz 1364 1598 1818 and 1994 which correspond to the Aβ1-42PGG complexes

S15

S32 ATD and CCS for Aβ1-42

Figure S5 ATDs of Aβ1-42 (10 microM) The peaks at mz 1128 (785 and 827 Aring2) and 1504 (643

and 696 Aring2) refer to the Aβ1-42 monomers with different conformations whereas the mz 1805

ATD reveals the presence of a dimer (1248 Aring2) a tetramer (2182 Aring2) a hexamer (2891 Aring2)

and a dodecamer (4640 Aring2)

S16

Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 6: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

from the simulations of Sgourakis et al The two most abundant structure families were

utilized The force field of PGG was built following the RESP ESP charge derive protocol

version III6 7 and some parameters were taken from the general Amber force field (GAFF) as

previously described8 The system containing one Aβ1-42 and one PGG was solvated in TIP3P9

water box using a spacing distance of 11 Aring Three additional Na+ ions were added to

neutralize the total charge Several minimization and heating cycles were performed to proper

equilibrate the system The MD simulation was performed in the NPT ensemble (ntp = 1 ntb

= 2) using the periodic boundary condition and a time step of 2 fs Temperature was regulated

by Langevin dynamics (ntt = 3) with a collision frequency of 10 The MD trajectories were

100-ns long for Complexes 1-2 and 200-ns long for Complexes 3-4 Two independent

trajectories were simulated

MM-GBSA The binding energy was evaluated using the molecular mechanics-

generalized Bornsurface area (MM-GBSA) module available in the Amber 12 package5

The solvation energy is represented by the generalized Born term (the polar part of the

solvation) plus a surface area term (the hydrophobic part of the solvation free energy)

S6

S2 Effect of PGG on early Aβ1-40 amyloid aggregation

S21 Mass spectra of Aβ1-40 and PGG mixtures

Figure S1 ESI-Q spectra of Aβ1-40 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-40PGG mixtures

The peaks are noted in brackets where the first number (in black) is the number of Aβ

molecules whereas the second number (in red) represents the number of bound PGG and the

charge is noted as a superscript The Aβ1-40 mass spectrum (Fig A) shows two major peaks at

mz 1081 and 1442 which refer to the Aβ monomers [1]-4 and [1]-3 respectively The minor

peak at mz 1731 correspond to Aβ dimer [2]-5 and tetramer [4]-10 species From the mass

spectrum obtained for the Aβ1-40PGG mixture at 11 molar ratio (Fig B) the most abundant

peaks of Aβ1-40 hetero complexes at mz 1318 and 1552 are attributed to the Aβ monomer with S7

one ([1+1]-4) and two ([1+2]-4) PGG molecules bound respectively The minor peaks at mz

1757 and 1920 refer to the monomer bonded to one PGG molecule ([1+1]-3) and dimer and

tetramer bonded to one and two PGG molecules ([2+1]-5 and [4+2]-10) respectively The

remaining Aβ1-40 homoligomers are the monomers at mz 1081([n]z = [1]-4) and 1442 ([n]z =

[1]-3) At Aβ1-40PGG 110 molar ratio (Fig C) the population of the heteroligomer peaks

increase at mz 1318 1552 1757 and 1920

S8

S22 Arrival Time Distributions (ATD) and Collision Cross Sections (CCS) for Aβ1-40

Figure S2 ATDs of Aβ1-40 (10 microM) The peak at mz 1081 refers to a single Aβ1-40 monomer

with a collision cross section of 750 Aring2 while two different conformations are found for the

peak at mz 1442 (621 Aring2 and 688 Aring2) The mz 1731 ATD displays larger and extended Aβ

oligomers a dimer (1156 Aring2) and a tetramer (2078 Aring2)

S9

Table S1 Collision cross section for homoligomers of Aβ1-40

mz n

Aβ1-40

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

1081 1 -4 750 621

1442 1 -3 621 621

1442 1 -3 688 621

1731 2 -5 1156 986

1731 4 -10 2078 1565

a values in Aring2

b given by σiso(n) = σAβ1-40mon n23

S10

S23 ATD and CCS for Aβ1-40 incubated with PGG

Figure S3 ATDs of Aβ1-40 (10 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 1318 and 1757 refer to Aβ1-40 monomers bound to one PGG molecule with cross

sections of 746 785 724 and 759 Aring2 whereas the mz 1553 ATD displays a compact and an

extended monomers bound to two PGG molecules with cross section of 851 and 901 Aring

respectively Dimer and tetramer complexes with one and two PGG molecules are also

detected at mz 1920 with cross sections of 1087 and 1762 Aring respectively

S11

Table S2 Collision cross section for heteroligomers of Aβ1-40 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-40

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

40ad

σiso(n)

Corrected Aβ1-40

ae

σcorr(nm)

1318 1 1 -4 746 706 1057152 621 656

1318 1 1 -4 785 706 1112419 621 691

1552 1 2 -4 851 786 1083349 621 673

1552 1 2 -4 901 786 1147000 621 712

1757 1 1 -3 724 706 1025976 621 637

1757 1 1 -3 759 706 1075574 621 668

1920 2 1 -5 1087 1054 1031260 986 1017

1920 4 2 -10 1762 1673 1053071 1565 1648

a values in Aring2

b isotropic cross section calculated as σiso(nm) = [n σAβ1-40mon32 + m σPGGmon

32]23 where

n and m are the number of Aβ1-40 and PGG molecules respectively and σAβ1-40mon (621 Aring2)

and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-40 monomer and

12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the collision

cross section of PGG (220 Aring2) was obtained from averaging the cross sections of geometry-

optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-40mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S12

S13

S3 Effect of PGG on early Aβ1-42 amyloid aggregation

S31 Mass spectra of Aβ1-42 and PGG mixtures

Figure S4 ESI-Q spectra of Aβ1-42 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-42PGG mixtures

The Aβ1-42 mass spectrum (Fig A) displays one major peak at mz 1504 which correspond to

the triply charged monomer [1]-3 whereas the minor peaks at mz 1128 and 1805 refer to Aβ

monomers [1]-4 and Aβ dimer tetramer hexamer and dodecamer ([2]-5 [4]-10 [6]-15 and [12]-

30) respectively The mass spectrum obtained for the Aβ1-42PGG mixture at 11 molar ratio

(Fig B) reveals the formation of different Aβ hetero complexes where the peaks at mz 1364

([1+1]-4) 1598 ([1+2]-4) 1818 ([1+1]-3) are attributed to the monomers bounded to one and

two PGG molecules whereas the peak at mz 1994 correspond to the complexes formed by S14

dimer tetramer and hexamer bounded to one two and three PGG molecules ([2+1]-5 ([4+2]-10

and ([6+3]-15) respectively The remaining homoligomer are the monomers at mz 1128

[1]-4 and 1504 [1]-3 At Aβ1-42PGG 110 molar ratio (Fig C) the population increase for the

peaks at mz 1364 1598 1818 and 1994 which correspond to the Aβ1-42PGG complexes

S15

S32 ATD and CCS for Aβ1-42

Figure S5 ATDs of Aβ1-42 (10 microM) The peaks at mz 1128 (785 and 827 Aring2) and 1504 (643

and 696 Aring2) refer to the Aβ1-42 monomers with different conformations whereas the mz 1805

ATD reveals the presence of a dimer (1248 Aring2) a tetramer (2182 Aring2) a hexamer (2891 Aring2)

and a dodecamer (4640 Aring2)

S16

Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 7: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

S2 Effect of PGG on early Aβ1-40 amyloid aggregation

S21 Mass spectra of Aβ1-40 and PGG mixtures

Figure S1 ESI-Q spectra of Aβ1-40 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-40PGG mixtures

The peaks are noted in brackets where the first number (in black) is the number of Aβ

molecules whereas the second number (in red) represents the number of bound PGG and the

charge is noted as a superscript The Aβ1-40 mass spectrum (Fig A) shows two major peaks at

mz 1081 and 1442 which refer to the Aβ monomers [1]-4 and [1]-3 respectively The minor

peak at mz 1731 correspond to Aβ dimer [2]-5 and tetramer [4]-10 species From the mass

spectrum obtained for the Aβ1-40PGG mixture at 11 molar ratio (Fig B) the most abundant

peaks of Aβ1-40 hetero complexes at mz 1318 and 1552 are attributed to the Aβ monomer with S7

one ([1+1]-4) and two ([1+2]-4) PGG molecules bound respectively The minor peaks at mz

1757 and 1920 refer to the monomer bonded to one PGG molecule ([1+1]-3) and dimer and

tetramer bonded to one and two PGG molecules ([2+1]-5 and [4+2]-10) respectively The

remaining Aβ1-40 homoligomers are the monomers at mz 1081([n]z = [1]-4) and 1442 ([n]z =

[1]-3) At Aβ1-40PGG 110 molar ratio (Fig C) the population of the heteroligomer peaks

increase at mz 1318 1552 1757 and 1920

S8

S22 Arrival Time Distributions (ATD) and Collision Cross Sections (CCS) for Aβ1-40

Figure S2 ATDs of Aβ1-40 (10 microM) The peak at mz 1081 refers to a single Aβ1-40 monomer

with a collision cross section of 750 Aring2 while two different conformations are found for the

peak at mz 1442 (621 Aring2 and 688 Aring2) The mz 1731 ATD displays larger and extended Aβ

oligomers a dimer (1156 Aring2) and a tetramer (2078 Aring2)

S9

Table S1 Collision cross section for homoligomers of Aβ1-40

mz n

Aβ1-40

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

1081 1 -4 750 621

1442 1 -3 621 621

1442 1 -3 688 621

1731 2 -5 1156 986

1731 4 -10 2078 1565

a values in Aring2

b given by σiso(n) = σAβ1-40mon n23

S10

S23 ATD and CCS for Aβ1-40 incubated with PGG

Figure S3 ATDs of Aβ1-40 (10 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 1318 and 1757 refer to Aβ1-40 monomers bound to one PGG molecule with cross

sections of 746 785 724 and 759 Aring2 whereas the mz 1553 ATD displays a compact and an

extended monomers bound to two PGG molecules with cross section of 851 and 901 Aring

respectively Dimer and tetramer complexes with one and two PGG molecules are also

detected at mz 1920 with cross sections of 1087 and 1762 Aring respectively

S11

Table S2 Collision cross section for heteroligomers of Aβ1-40 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-40

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

40ad

σiso(n)

Corrected Aβ1-40

ae

σcorr(nm)

1318 1 1 -4 746 706 1057152 621 656

1318 1 1 -4 785 706 1112419 621 691

1552 1 2 -4 851 786 1083349 621 673

1552 1 2 -4 901 786 1147000 621 712

1757 1 1 -3 724 706 1025976 621 637

1757 1 1 -3 759 706 1075574 621 668

1920 2 1 -5 1087 1054 1031260 986 1017

1920 4 2 -10 1762 1673 1053071 1565 1648

a values in Aring2

b isotropic cross section calculated as σiso(nm) = [n σAβ1-40mon32 + m σPGGmon

32]23 where

n and m are the number of Aβ1-40 and PGG molecules respectively and σAβ1-40mon (621 Aring2)

and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-40 monomer and

12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the collision

cross section of PGG (220 Aring2) was obtained from averaging the cross sections of geometry-

optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-40mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S12

S13

S3 Effect of PGG on early Aβ1-42 amyloid aggregation

S31 Mass spectra of Aβ1-42 and PGG mixtures

Figure S4 ESI-Q spectra of Aβ1-42 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-42PGG mixtures

The Aβ1-42 mass spectrum (Fig A) displays one major peak at mz 1504 which correspond to

the triply charged monomer [1]-3 whereas the minor peaks at mz 1128 and 1805 refer to Aβ

monomers [1]-4 and Aβ dimer tetramer hexamer and dodecamer ([2]-5 [4]-10 [6]-15 and [12]-

30) respectively The mass spectrum obtained for the Aβ1-42PGG mixture at 11 molar ratio

(Fig B) reveals the formation of different Aβ hetero complexes where the peaks at mz 1364

([1+1]-4) 1598 ([1+2]-4) 1818 ([1+1]-3) are attributed to the monomers bounded to one and

two PGG molecules whereas the peak at mz 1994 correspond to the complexes formed by S14

dimer tetramer and hexamer bounded to one two and three PGG molecules ([2+1]-5 ([4+2]-10

and ([6+3]-15) respectively The remaining homoligomer are the monomers at mz 1128

[1]-4 and 1504 [1]-3 At Aβ1-42PGG 110 molar ratio (Fig C) the population increase for the

peaks at mz 1364 1598 1818 and 1994 which correspond to the Aβ1-42PGG complexes

S15

S32 ATD and CCS for Aβ1-42

Figure S5 ATDs of Aβ1-42 (10 microM) The peaks at mz 1128 (785 and 827 Aring2) and 1504 (643

and 696 Aring2) refer to the Aβ1-42 monomers with different conformations whereas the mz 1805

ATD reveals the presence of a dimer (1248 Aring2) a tetramer (2182 Aring2) a hexamer (2891 Aring2)

and a dodecamer (4640 Aring2)

S16

Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 8: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

one ([1+1]-4) and two ([1+2]-4) PGG molecules bound respectively The minor peaks at mz

1757 and 1920 refer to the monomer bonded to one PGG molecule ([1+1]-3) and dimer and

tetramer bonded to one and two PGG molecules ([2+1]-5 and [4+2]-10) respectively The

remaining Aβ1-40 homoligomers are the monomers at mz 1081([n]z = [1]-4) and 1442 ([n]z =

[1]-3) At Aβ1-40PGG 110 molar ratio (Fig C) the population of the heteroligomer peaks

increase at mz 1318 1552 1757 and 1920

S8

S22 Arrival Time Distributions (ATD) and Collision Cross Sections (CCS) for Aβ1-40

Figure S2 ATDs of Aβ1-40 (10 microM) The peak at mz 1081 refers to a single Aβ1-40 monomer

with a collision cross section of 750 Aring2 while two different conformations are found for the

peak at mz 1442 (621 Aring2 and 688 Aring2) The mz 1731 ATD displays larger and extended Aβ

oligomers a dimer (1156 Aring2) and a tetramer (2078 Aring2)

S9

Table S1 Collision cross section for homoligomers of Aβ1-40

mz n

Aβ1-40

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

1081 1 -4 750 621

1442 1 -3 621 621

1442 1 -3 688 621

1731 2 -5 1156 986

1731 4 -10 2078 1565

a values in Aring2

b given by σiso(n) = σAβ1-40mon n23

S10

S23 ATD and CCS for Aβ1-40 incubated with PGG

Figure S3 ATDs of Aβ1-40 (10 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 1318 and 1757 refer to Aβ1-40 monomers bound to one PGG molecule with cross

sections of 746 785 724 and 759 Aring2 whereas the mz 1553 ATD displays a compact and an

extended monomers bound to two PGG molecules with cross section of 851 and 901 Aring

respectively Dimer and tetramer complexes with one and two PGG molecules are also

detected at mz 1920 with cross sections of 1087 and 1762 Aring respectively

S11

Table S2 Collision cross section for heteroligomers of Aβ1-40 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-40

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

40ad

σiso(n)

Corrected Aβ1-40

ae

σcorr(nm)

1318 1 1 -4 746 706 1057152 621 656

1318 1 1 -4 785 706 1112419 621 691

1552 1 2 -4 851 786 1083349 621 673

1552 1 2 -4 901 786 1147000 621 712

1757 1 1 -3 724 706 1025976 621 637

1757 1 1 -3 759 706 1075574 621 668

1920 2 1 -5 1087 1054 1031260 986 1017

1920 4 2 -10 1762 1673 1053071 1565 1648

a values in Aring2

b isotropic cross section calculated as σiso(nm) = [n σAβ1-40mon32 + m σPGGmon

32]23 where

n and m are the number of Aβ1-40 and PGG molecules respectively and σAβ1-40mon (621 Aring2)

and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-40 monomer and

12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the collision

cross section of PGG (220 Aring2) was obtained from averaging the cross sections of geometry-

optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-40mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S12

S13

S3 Effect of PGG on early Aβ1-42 amyloid aggregation

S31 Mass spectra of Aβ1-42 and PGG mixtures

Figure S4 ESI-Q spectra of Aβ1-42 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-42PGG mixtures

The Aβ1-42 mass spectrum (Fig A) displays one major peak at mz 1504 which correspond to

the triply charged monomer [1]-3 whereas the minor peaks at mz 1128 and 1805 refer to Aβ

monomers [1]-4 and Aβ dimer tetramer hexamer and dodecamer ([2]-5 [4]-10 [6]-15 and [12]-

30) respectively The mass spectrum obtained for the Aβ1-42PGG mixture at 11 molar ratio

(Fig B) reveals the formation of different Aβ hetero complexes where the peaks at mz 1364

([1+1]-4) 1598 ([1+2]-4) 1818 ([1+1]-3) are attributed to the monomers bounded to one and

two PGG molecules whereas the peak at mz 1994 correspond to the complexes formed by S14

dimer tetramer and hexamer bounded to one two and three PGG molecules ([2+1]-5 ([4+2]-10

and ([6+3]-15) respectively The remaining homoligomer are the monomers at mz 1128

[1]-4 and 1504 [1]-3 At Aβ1-42PGG 110 molar ratio (Fig C) the population increase for the

peaks at mz 1364 1598 1818 and 1994 which correspond to the Aβ1-42PGG complexes

S15

S32 ATD and CCS for Aβ1-42

Figure S5 ATDs of Aβ1-42 (10 microM) The peaks at mz 1128 (785 and 827 Aring2) and 1504 (643

and 696 Aring2) refer to the Aβ1-42 monomers with different conformations whereas the mz 1805

ATD reveals the presence of a dimer (1248 Aring2) a tetramer (2182 Aring2) a hexamer (2891 Aring2)

and a dodecamer (4640 Aring2)

S16

Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

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S22 Arrival Time Distributions (ATD) and Collision Cross Sections (CCS) for Aβ1-40

Figure S2 ATDs of Aβ1-40 (10 microM) The peak at mz 1081 refers to a single Aβ1-40 monomer

with a collision cross section of 750 Aring2 while two different conformations are found for the

peak at mz 1442 (621 Aring2 and 688 Aring2) The mz 1731 ATD displays larger and extended Aβ

oligomers a dimer (1156 Aring2) and a tetramer (2078 Aring2)

S9

Table S1 Collision cross section for homoligomers of Aβ1-40

mz n

Aβ1-40

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

1081 1 -4 750 621

1442 1 -3 621 621

1442 1 -3 688 621

1731 2 -5 1156 986

1731 4 -10 2078 1565

a values in Aring2

b given by σiso(n) = σAβ1-40mon n23

S10

S23 ATD and CCS for Aβ1-40 incubated with PGG

Figure S3 ATDs of Aβ1-40 (10 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 1318 and 1757 refer to Aβ1-40 monomers bound to one PGG molecule with cross

sections of 746 785 724 and 759 Aring2 whereas the mz 1553 ATD displays a compact and an

extended monomers bound to two PGG molecules with cross section of 851 and 901 Aring

respectively Dimer and tetramer complexes with one and two PGG molecules are also

detected at mz 1920 with cross sections of 1087 and 1762 Aring respectively

S11

Table S2 Collision cross section for heteroligomers of Aβ1-40 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-40

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

40ad

σiso(n)

Corrected Aβ1-40

ae

σcorr(nm)

1318 1 1 -4 746 706 1057152 621 656

1318 1 1 -4 785 706 1112419 621 691

1552 1 2 -4 851 786 1083349 621 673

1552 1 2 -4 901 786 1147000 621 712

1757 1 1 -3 724 706 1025976 621 637

1757 1 1 -3 759 706 1075574 621 668

1920 2 1 -5 1087 1054 1031260 986 1017

1920 4 2 -10 1762 1673 1053071 1565 1648

a values in Aring2

b isotropic cross section calculated as σiso(nm) = [n σAβ1-40mon32 + m σPGGmon

32]23 where

n and m are the number of Aβ1-40 and PGG molecules respectively and σAβ1-40mon (621 Aring2)

and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-40 monomer and

12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the collision

cross section of PGG (220 Aring2) was obtained from averaging the cross sections of geometry-

optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-40mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S12

S13

S3 Effect of PGG on early Aβ1-42 amyloid aggregation

S31 Mass spectra of Aβ1-42 and PGG mixtures

Figure S4 ESI-Q spectra of Aβ1-42 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-42PGG mixtures

The Aβ1-42 mass spectrum (Fig A) displays one major peak at mz 1504 which correspond to

the triply charged monomer [1]-3 whereas the minor peaks at mz 1128 and 1805 refer to Aβ

monomers [1]-4 and Aβ dimer tetramer hexamer and dodecamer ([2]-5 [4]-10 [6]-15 and [12]-

30) respectively The mass spectrum obtained for the Aβ1-42PGG mixture at 11 molar ratio

(Fig B) reveals the formation of different Aβ hetero complexes where the peaks at mz 1364

([1+1]-4) 1598 ([1+2]-4) 1818 ([1+1]-3) are attributed to the monomers bounded to one and

two PGG molecules whereas the peak at mz 1994 correspond to the complexes formed by S14

dimer tetramer and hexamer bounded to one two and three PGG molecules ([2+1]-5 ([4+2]-10

and ([6+3]-15) respectively The remaining homoligomer are the monomers at mz 1128

[1]-4 and 1504 [1]-3 At Aβ1-42PGG 110 molar ratio (Fig C) the population increase for the

peaks at mz 1364 1598 1818 and 1994 which correspond to the Aβ1-42PGG complexes

S15

S32 ATD and CCS for Aβ1-42

Figure S5 ATDs of Aβ1-42 (10 microM) The peaks at mz 1128 (785 and 827 Aring2) and 1504 (643

and 696 Aring2) refer to the Aβ1-42 monomers with different conformations whereas the mz 1805

ATD reveals the presence of a dimer (1248 Aring2) a tetramer (2182 Aring2) a hexamer (2891 Aring2)

and a dodecamer (4640 Aring2)

S16

Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 10: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

Table S1 Collision cross section for homoligomers of Aβ1-40

mz n

Aβ1-40

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

1081 1 -4 750 621

1442 1 -3 621 621

1442 1 -3 688 621

1731 2 -5 1156 986

1731 4 -10 2078 1565

a values in Aring2

b given by σiso(n) = σAβ1-40mon n23

S10

S23 ATD and CCS for Aβ1-40 incubated with PGG

Figure S3 ATDs of Aβ1-40 (10 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 1318 and 1757 refer to Aβ1-40 monomers bound to one PGG molecule with cross

sections of 746 785 724 and 759 Aring2 whereas the mz 1553 ATD displays a compact and an

extended monomers bound to two PGG molecules with cross section of 851 and 901 Aring

respectively Dimer and tetramer complexes with one and two PGG molecules are also

detected at mz 1920 with cross sections of 1087 and 1762 Aring respectively

S11

Table S2 Collision cross section for heteroligomers of Aβ1-40 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-40

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

40ad

σiso(n)

Corrected Aβ1-40

ae

σcorr(nm)

1318 1 1 -4 746 706 1057152 621 656

1318 1 1 -4 785 706 1112419 621 691

1552 1 2 -4 851 786 1083349 621 673

1552 1 2 -4 901 786 1147000 621 712

1757 1 1 -3 724 706 1025976 621 637

1757 1 1 -3 759 706 1075574 621 668

1920 2 1 -5 1087 1054 1031260 986 1017

1920 4 2 -10 1762 1673 1053071 1565 1648

a values in Aring2

b isotropic cross section calculated as σiso(nm) = [n σAβ1-40mon32 + m σPGGmon

32]23 where

n and m are the number of Aβ1-40 and PGG molecules respectively and σAβ1-40mon (621 Aring2)

and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-40 monomer and

12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the collision

cross section of PGG (220 Aring2) was obtained from averaging the cross sections of geometry-

optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-40mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S12

S13

S3 Effect of PGG on early Aβ1-42 amyloid aggregation

S31 Mass spectra of Aβ1-42 and PGG mixtures

Figure S4 ESI-Q spectra of Aβ1-42 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-42PGG mixtures

The Aβ1-42 mass spectrum (Fig A) displays one major peak at mz 1504 which correspond to

the triply charged monomer [1]-3 whereas the minor peaks at mz 1128 and 1805 refer to Aβ

monomers [1]-4 and Aβ dimer tetramer hexamer and dodecamer ([2]-5 [4]-10 [6]-15 and [12]-

30) respectively The mass spectrum obtained for the Aβ1-42PGG mixture at 11 molar ratio

(Fig B) reveals the formation of different Aβ hetero complexes where the peaks at mz 1364

([1+1]-4) 1598 ([1+2]-4) 1818 ([1+1]-3) are attributed to the monomers bounded to one and

two PGG molecules whereas the peak at mz 1994 correspond to the complexes formed by S14

dimer tetramer and hexamer bounded to one two and three PGG molecules ([2+1]-5 ([4+2]-10

and ([6+3]-15) respectively The remaining homoligomer are the monomers at mz 1128

[1]-4 and 1504 [1]-3 At Aβ1-42PGG 110 molar ratio (Fig C) the population increase for the

peaks at mz 1364 1598 1818 and 1994 which correspond to the Aβ1-42PGG complexes

S15

S32 ATD and CCS for Aβ1-42

Figure S5 ATDs of Aβ1-42 (10 microM) The peaks at mz 1128 (785 and 827 Aring2) and 1504 (643

and 696 Aring2) refer to the Aβ1-42 monomers with different conformations whereas the mz 1805

ATD reveals the presence of a dimer (1248 Aring2) a tetramer (2182 Aring2) a hexamer (2891 Aring2)

and a dodecamer (4640 Aring2)

S16

Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 11: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

S23 ATD and CCS for Aβ1-40 incubated with PGG

Figure S3 ATDs of Aβ1-40 (10 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 1318 and 1757 refer to Aβ1-40 monomers bound to one PGG molecule with cross

sections of 746 785 724 and 759 Aring2 whereas the mz 1553 ATD displays a compact and an

extended monomers bound to two PGG molecules with cross section of 851 and 901 Aring

respectively Dimer and tetramer complexes with one and two PGG molecules are also

detected at mz 1920 with cross sections of 1087 and 1762 Aring respectively

S11

Table S2 Collision cross section for heteroligomers of Aβ1-40 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-40

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

40ad

σiso(n)

Corrected Aβ1-40

ae

σcorr(nm)

1318 1 1 -4 746 706 1057152 621 656

1318 1 1 -4 785 706 1112419 621 691

1552 1 2 -4 851 786 1083349 621 673

1552 1 2 -4 901 786 1147000 621 712

1757 1 1 -3 724 706 1025976 621 637

1757 1 1 -3 759 706 1075574 621 668

1920 2 1 -5 1087 1054 1031260 986 1017

1920 4 2 -10 1762 1673 1053071 1565 1648

a values in Aring2

b isotropic cross section calculated as σiso(nm) = [n σAβ1-40mon32 + m σPGGmon

32]23 where

n and m are the number of Aβ1-40 and PGG molecules respectively and σAβ1-40mon (621 Aring2)

and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-40 monomer and

12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the collision

cross section of PGG (220 Aring2) was obtained from averaging the cross sections of geometry-

optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-40mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S12

S13

S3 Effect of PGG on early Aβ1-42 amyloid aggregation

S31 Mass spectra of Aβ1-42 and PGG mixtures

Figure S4 ESI-Q spectra of Aβ1-42 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-42PGG mixtures

The Aβ1-42 mass spectrum (Fig A) displays one major peak at mz 1504 which correspond to

the triply charged monomer [1]-3 whereas the minor peaks at mz 1128 and 1805 refer to Aβ

monomers [1]-4 and Aβ dimer tetramer hexamer and dodecamer ([2]-5 [4]-10 [6]-15 and [12]-

30) respectively The mass spectrum obtained for the Aβ1-42PGG mixture at 11 molar ratio

(Fig B) reveals the formation of different Aβ hetero complexes where the peaks at mz 1364

([1+1]-4) 1598 ([1+2]-4) 1818 ([1+1]-3) are attributed to the monomers bounded to one and

two PGG molecules whereas the peak at mz 1994 correspond to the complexes formed by S14

dimer tetramer and hexamer bounded to one two and three PGG molecules ([2+1]-5 ([4+2]-10

and ([6+3]-15) respectively The remaining homoligomer are the monomers at mz 1128

[1]-4 and 1504 [1]-3 At Aβ1-42PGG 110 molar ratio (Fig C) the population increase for the

peaks at mz 1364 1598 1818 and 1994 which correspond to the Aβ1-42PGG complexes

S15

S32 ATD and CCS for Aβ1-42

Figure S5 ATDs of Aβ1-42 (10 microM) The peaks at mz 1128 (785 and 827 Aring2) and 1504 (643

and 696 Aring2) refer to the Aβ1-42 monomers with different conformations whereas the mz 1805

ATD reveals the presence of a dimer (1248 Aring2) a tetramer (2182 Aring2) a hexamer (2891 Aring2)

and a dodecamer (4640 Aring2)

S16

Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 12: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

Table S2 Collision cross section for heteroligomers of Aβ1-40 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-40

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

40ad

σiso(n)

Corrected Aβ1-40

ae

σcorr(nm)

1318 1 1 -4 746 706 1057152 621 656

1318 1 1 -4 785 706 1112419 621 691

1552 1 2 -4 851 786 1083349 621 673

1552 1 2 -4 901 786 1147000 621 712

1757 1 1 -3 724 706 1025976 621 637

1757 1 1 -3 759 706 1075574 621 668

1920 2 1 -5 1087 1054 1031260 986 1017

1920 4 2 -10 1762 1673 1053071 1565 1648

a values in Aring2

b isotropic cross section calculated as σiso(nm) = [n σAβ1-40mon32 + m σPGGmon

32]23 where

n and m are the number of Aβ1-40 and PGG molecules respectively and σAβ1-40mon (621 Aring2)

and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-40 monomer and

12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the collision

cross section of PGG (220 Aring2) was obtained from averaging the cross sections of geometry-

optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-40mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S12

S13

S3 Effect of PGG on early Aβ1-42 amyloid aggregation

S31 Mass spectra of Aβ1-42 and PGG mixtures

Figure S4 ESI-Q spectra of Aβ1-42 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-42PGG mixtures

The Aβ1-42 mass spectrum (Fig A) displays one major peak at mz 1504 which correspond to

the triply charged monomer [1]-3 whereas the minor peaks at mz 1128 and 1805 refer to Aβ

monomers [1]-4 and Aβ dimer tetramer hexamer and dodecamer ([2]-5 [4]-10 [6]-15 and [12]-

30) respectively The mass spectrum obtained for the Aβ1-42PGG mixture at 11 molar ratio

(Fig B) reveals the formation of different Aβ hetero complexes where the peaks at mz 1364

([1+1]-4) 1598 ([1+2]-4) 1818 ([1+1]-3) are attributed to the monomers bounded to one and

two PGG molecules whereas the peak at mz 1994 correspond to the complexes formed by S14

dimer tetramer and hexamer bounded to one two and three PGG molecules ([2+1]-5 ([4+2]-10

and ([6+3]-15) respectively The remaining homoligomer are the monomers at mz 1128

[1]-4 and 1504 [1]-3 At Aβ1-42PGG 110 molar ratio (Fig C) the population increase for the

peaks at mz 1364 1598 1818 and 1994 which correspond to the Aβ1-42PGG complexes

S15

S32 ATD and CCS for Aβ1-42

Figure S5 ATDs of Aβ1-42 (10 microM) The peaks at mz 1128 (785 and 827 Aring2) and 1504 (643

and 696 Aring2) refer to the Aβ1-42 monomers with different conformations whereas the mz 1805

ATD reveals the presence of a dimer (1248 Aring2) a tetramer (2182 Aring2) a hexamer (2891 Aring2)

and a dodecamer (4640 Aring2)

S16

Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

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S13

S3 Effect of PGG on early Aβ1-42 amyloid aggregation

S31 Mass spectra of Aβ1-42 and PGG mixtures

Figure S4 ESI-Q spectra of Aβ1-42 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-42PGG mixtures

The Aβ1-42 mass spectrum (Fig A) displays one major peak at mz 1504 which correspond to

the triply charged monomer [1]-3 whereas the minor peaks at mz 1128 and 1805 refer to Aβ

monomers [1]-4 and Aβ dimer tetramer hexamer and dodecamer ([2]-5 [4]-10 [6]-15 and [12]-

30) respectively The mass spectrum obtained for the Aβ1-42PGG mixture at 11 molar ratio

(Fig B) reveals the formation of different Aβ hetero complexes where the peaks at mz 1364

([1+1]-4) 1598 ([1+2]-4) 1818 ([1+1]-3) are attributed to the monomers bounded to one and

two PGG molecules whereas the peak at mz 1994 correspond to the complexes formed by S14

dimer tetramer and hexamer bounded to one two and three PGG molecules ([2+1]-5 ([4+2]-10

and ([6+3]-15) respectively The remaining homoligomer are the monomers at mz 1128

[1]-4 and 1504 [1]-3 At Aβ1-42PGG 110 molar ratio (Fig C) the population increase for the

peaks at mz 1364 1598 1818 and 1994 which correspond to the Aβ1-42PGG complexes

S15

S32 ATD and CCS for Aβ1-42

Figure S5 ATDs of Aβ1-42 (10 microM) The peaks at mz 1128 (785 and 827 Aring2) and 1504 (643

and 696 Aring2) refer to the Aβ1-42 monomers with different conformations whereas the mz 1805

ATD reveals the presence of a dimer (1248 Aring2) a tetramer (2182 Aring2) a hexamer (2891 Aring2)

and a dodecamer (4640 Aring2)

S16

Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 14: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

S3 Effect of PGG on early Aβ1-42 amyloid aggregation

S31 Mass spectra of Aβ1-42 and PGG mixtures

Figure S4 ESI-Q spectra of Aβ1-42 incubated (A) in buffer solution (10 mM of

ammonium acetate pH 74) (B) with PGG at 11 and (C) at 110 Aβ1-42PGG mixtures

The Aβ1-42 mass spectrum (Fig A) displays one major peak at mz 1504 which correspond to

the triply charged monomer [1]-3 whereas the minor peaks at mz 1128 and 1805 refer to Aβ

monomers [1]-4 and Aβ dimer tetramer hexamer and dodecamer ([2]-5 [4]-10 [6]-15 and [12]-

30) respectively The mass spectrum obtained for the Aβ1-42PGG mixture at 11 molar ratio

(Fig B) reveals the formation of different Aβ hetero complexes where the peaks at mz 1364

([1+1]-4) 1598 ([1+2]-4) 1818 ([1+1]-3) are attributed to the monomers bounded to one and

two PGG molecules whereas the peak at mz 1994 correspond to the complexes formed by S14

dimer tetramer and hexamer bounded to one two and three PGG molecules ([2+1]-5 ([4+2]-10

and ([6+3]-15) respectively The remaining homoligomer are the monomers at mz 1128

[1]-4 and 1504 [1]-3 At Aβ1-42PGG 110 molar ratio (Fig C) the population increase for the

peaks at mz 1364 1598 1818 and 1994 which correspond to the Aβ1-42PGG complexes

S15

S32 ATD and CCS for Aβ1-42

Figure S5 ATDs of Aβ1-42 (10 microM) The peaks at mz 1128 (785 and 827 Aring2) and 1504 (643

and 696 Aring2) refer to the Aβ1-42 monomers with different conformations whereas the mz 1805

ATD reveals the presence of a dimer (1248 Aring2) a tetramer (2182 Aring2) a hexamer (2891 Aring2)

and a dodecamer (4640 Aring2)

S16

Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 15: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

dimer tetramer and hexamer bounded to one two and three PGG molecules ([2+1]-5 ([4+2]-10

and ([6+3]-15) respectively The remaining homoligomer are the monomers at mz 1128

[1]-4 and 1504 [1]-3 At Aβ1-42PGG 110 molar ratio (Fig C) the population increase for the

peaks at mz 1364 1598 1818 and 1994 which correspond to the Aβ1-42PGG complexes

S15

S32 ATD and CCS for Aβ1-42

Figure S5 ATDs of Aβ1-42 (10 microM) The peaks at mz 1128 (785 and 827 Aring2) and 1504 (643

and 696 Aring2) refer to the Aβ1-42 monomers with different conformations whereas the mz 1805

ATD reveals the presence of a dimer (1248 Aring2) a tetramer (2182 Aring2) a hexamer (2891 Aring2)

and a dodecamer (4640 Aring2)

S16

Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 16: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

S32 ATD and CCS for Aβ1-42

Figure S5 ATDs of Aβ1-42 (10 microM) The peaks at mz 1128 (785 and 827 Aring2) and 1504 (643

and 696 Aring2) refer to the Aβ1-42 monomers with different conformations whereas the mz 1805

ATD reveals the presence of a dimer (1248 Aring2) a tetramer (2182 Aring2) a hexamer (2891 Aring2)

and a dodecamer (4640 Aring2)

S16

Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

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Table S3 Collision cross section for homoligomers of Aβ1-42

mz n

Aβ1-42

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

1128 1 -4 785 643

1128 1 -4 827 643

1504 1 -3 643 643

1504 1 -3 696 643

1805 2 -5 1248 1021

1805 4 -10 2182 1620

1805 6 -15 2891 2123

1805 12 -30 4640 3370

a values in Aring2

b given by σiso(n) = σAβ1-42mon n23

S17

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 18: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

S33 ATD and CCS for Aβ1-42 incubated with PGG

Figure S6 ATDs of Aβ1-42 (10 microM) incubated with PGG at the molar ratio of 11 The

mz 1364 and 1818 ATD show the formation of Aβ1-42 monomers bound to one PGG

molecule with cross sections of 848 879 734 and 804 Aring2 while the peak at mz 1599 refer to

Aβ1-40 monomers bound to two PGG molecule with cross sections of 958 and 993 Aring2 Dimer

tetramer and hexamer heteroligomers are observed at mz 1994 with cross sections of 1157

1856 and 2352 Aring2 respectively

S18

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 19: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

Table S4 Collision cross section for heteroligomers of Aβ1-42 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-42

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

42ad

σiso(n)

Corrected Aβ1-42

ae

σcorr(nm)

1364 1 1 -4 848 726 1167500 643 751

1364 1 1 -4 879 726 1210179 643 778

1598 1 2 -4 958 805 1189857 643 765

1598 1 2 -4 993 805 1233328 643 793

1818 1 1 -3 734 726 1010548 643 650

1818 1 1 -3 804 726 1106922 643 712

1994 2 1 -5 1157 1088 1063565 1021 1086

1994 4 2 -10 1856 1727 1074786 1620 1741

1994 6 3 -15 2352 2263 1039410 2123 2207

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-42mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-42 and PGG molecules respectively and σAβ1-42mon

(643 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-42 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-42mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S19

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 20: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

S20

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 21: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

S4 Effect of PGG on early Aβ1-11 amyloid aggregation

S41 Mass spectra of Aβ1-11 and PGG mixtures

Figure S7 ESI-Q spectra of Aβ1-11 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ1-11PGG mixtures The Aβ1-11 mass spectrum (Fig A) shows two major peaks at

mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and [4]-4) and one minor peak at mz 883 ([2]-3)

while the mass spectrum collected for the Aβ1-11PGG mixture at 11 molar ratio (Fig B)

reveals the presence of the Aβ homoligomers at mz 663 ([1]-2) and 1325 ([1]-1 [2]-2 [3]-3 and

[4]-4) The others peaks at mz 945 ([5+2]-9) 1069 ([1+2]-3) 1133 ([1+1]-2) 1197 ([2+1]-3)

1261

([5+1]-6) 1387 ([8+2]-9) 1513 ([5+1]-5) 1594 ([7+2]-7) 1663 ([9+5]-10) 1743 ([9+4]-9) and

1863 ([7+4]-7) are attributed to the multiple complexes formed between Aβ1-11 and PGG

S21

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 22: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

which involves the formation of Aβ heteroligomers up to nonamers At Aβ1-11PGG 110 ratio

(Fig C) the peaks of Aβ1-11PGG complexes become more abundant remaining just the Aβ1-

11 homoligomer at mz 663 ([1]-2)

S22

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 23: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

S42 ATD and CCS for Aβ1-11

Figure S8 ATDs of Aβ1-11 (100 microM) The peak at mz 663 refer to the Aβ1-11 monomer with

cross section of 254 Aring2 which is consistent with the cross section of a compact monomer

(248 Aring2) obtained from the mz 1325 ATD that also contains a dimer (398 Aring2) a trimer (518

Aring2) and a tetramer (640 Aring2) The mz 883 ATD shows two different confirmations for Aβ

dimer a compact (414 Aring2) and an extended (598 Aring2)

S23

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 24: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

Table S5 Collision cross section for homoligomers of Aβ1-11

mz n

Aβ1-11

z

charge

Experimental cross sectiona

σexp

Idealized growth model

Isotropicab σiso(n)

663 1 -2 254 248

883 2 -3 414 394

883 2 -3 598 394

1325 1 -1 248 248

1325 2 -2 398 394

1325 3 -3 518 516

1325 4 -4 640 625

a values in Aring2

b given by σiso(n) = σAβ1-11mon n23

S24

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 25: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

S43 ATD and CCS for Aβ1-11 incubated with PGG

Figure S9 ATDs of Aβ1-11 (100 microM) incubated with PGG at the molar ratio of 11 The

data show ATDs for Aβ1-11 monomer bound to one and two PGG molecules at mz 1133 (378

and 415 Aring2) and 1069 (494 and 537 Aring2) respectively The peak at mz 1197 refers to Aβ

dimers bound to one PGG molecule with cross sections of 502 and 548 Aring2 whereas pentamer

complexes are observed at mz 945 (895 and 1004 Aring2) 1261 (815 and 856 Aring2) and 1513 (807

S25

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 26: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

and 843 Aring2) The other peaks are mz 1387 1594 1663 1743 and 1863 refer to octamers

(1137 and 1204 Aring) heptamers (1064 and 1158 Aring) nonamers (1395 and 1432 Aring) nonamers

(1328 and 1362 Aring) and heptamers (1184 and 1227 Aring) respectively

S26

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 27: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

Table S6 Collision cross section for heteroligomers of Aβ1-11 incubated with PGG at the

molar ratio of 11

mz n

Aβ1-11

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ1-

11ad

σiso(n)

Corrected Aβ1-11

ae

σcorr(nm)

945 5 2 -9 895 879 1017995 725 738

945 5 2 -9 1004 879 1141975 725 828

1069 1 2 -3 494 478 1033747 248 256

1069 1 2 -3 537 478 1123729 248 279

1133 1 1 -2 378 372 1016025 248 252

1133 1 1 -2 415 372 1115477 248 277

1197 2 1 -3 502 497 1009962 394 398

1197 2 1 -3 548 497 1122508 394 434

1261 5 1 -6 815 804 1013662 725 735

1261 5 1 -6 856 804 1064656 725 772

1387 8 2 -9 1137 1126 1009751 992 1002

1387 8 2 -9 1204 1126 1069252 992 1061

1513 5 1 -5 807 804 1003711 725 728

1513 5 1 -5 843 804 1048487 725 760

1594 7 2 -7 1064 1047 1016210 908 922

1594 7 2 -7 1158 1047 1105988 908 1004

1663 9 5 -10 1395 1384 1007763 1073 1081

1663 9 5 -10 1432 1384 1034492 1073 1110

1743 9 4 -9 1328 1325 1002254 1073 1075

1743 9 4 -9 1362 1325 1027914 1073 1103

1863 7 4 -7 1184 1178 1005274 908 912

1863 7 4 -7 1227 1178 1041783 908 945

a values in Aring2

S27

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 28: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

b isotropic cross section is calculated as σiso(nm) = [n σAβ1-11mon32 + m σPGGmon

32]23

where n and m are the number of Aβ1-11 and PGG molecules respectively and σAβ1-11mon

(248 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ1-11 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ1-11mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S28

S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

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S5 Effect of PGG on early Aβ11-22 amyloid aggregation

S51 Mass spectra of Aβ11-22 and PGG mixtures

Figure S10 ESI-Q spectra of Aβ11-22 incubated (A) in water (B) with PGG at 11 and (C)

at 110 Aβ11-22PGG mixtures The Aβ11-22 mass spectrum (Fig A) displays two major peaks

at mz 495 and 742 that refer to the Aβ monomers triply ([1]+3) and doubly ([1]+2) charged

respectively Four minor peaks are observed at mz 989 ([2]+3) 1113 ([3]+4) 1187 ([4]+5) and

1484 ([1]+1 [2]+2 and [3]+3) which denote the formation of monomers dimers trimers and

tetramers From the mass spectrum obtained for the Aβ11-22PGG mixture at 11 molar ratio

(Fig B) the peaks at mz 808 ([1+1]+3) 836 ([5+1]+10) 1033 ([5+2]+9) 1079 ([3+1]+5) 1212

([1+1]+2) 1303 ([2+1]+3) 1430 ([9+1]+10) 1541 ([6+2]+7) 1683 ([1+2]+2) 1753 ([7+2]+7)

S29

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 30: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

1781 ([7+6]+9) and 1902 ([9+4]+9) are attributed to the multiple Aβ1-11PGG complexes

contemplating the formation of Aβ heteroligomers up to nonamers At Aβ11-22PGG 110 ratio

(Fig C) the peaks of the Aβ heteroligomers become more abundant remaining just the Aβ11-

22 homoligomers at mz 495 ([1]+3) 742 ([1]+2) and 1113 ([3]+4)

S30

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 31: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

S52 ATD and CCS for Aβ11-22

Figure S11 ATDs of Aβ11-22 (100 microM) The peaks at mz 495 and 742 are the most abundant

which refer to Aβ monomer species with cross sections of 344 and 308 Aring2 respectively The

other peaks are mz 989 (dimers 518 and 715 Aring2) 1113 (trimers 704 and 762 Aring2) 1187

(tetramers 786 and 846 Aring2) and 1484 (monomer 301 Aring2 dimer 493 Aring2 trimer 653 Aring2)

S31

Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

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Table S7 Collision cross section for homoligomers of Aβ11-22

mz n

Aβ11-22

z

charge

Experimental cross sectiona

σexp

Idealized growth model

isotropicab σiso(n)

495 1 +3 344 301

742 1 +2 308 301

989 2 +3 518 478

989 2 +3 715 478

1113 3 +4 704 626

1113 3 +4 762 626

1187 4 +5 786 758

1187 4 +5 846 758

1484 1 +1 301 301

1484 2 +2 493 478

1484 3 +3 653 626

a values in Aring2

b given by σiso(n) = σAβ11-22mon n23

S32

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 33: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

S53 ATD and CCS for Aβ11-22 incubated with PGG

Figure S12 ATDs of Aβ11-22 (100 microM) incubated with PGG at the molar ratio of 11 The

peaks at mz 808 1212 and 1683 indicate the formation of Aβ11-22 monomers complexed with

one (510 Aring2) one (431 and 494 Aring2) and two (543 and 640 Aring2) PGG molecules respectively

while a dimer and a trimer bound to one PGG molecule are found at mz 1303 (580 Aring2) and

1079 (716 Aring2) respectively The ATDs obtained for mz 836 (975 and 1098 Aring2) and 1033

S33

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 34: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

(1040 and 1132 Aring2) reveal the presence of pentamers bound to one and two PGG molecules

respectively The other peaks at mz 1430 1541 1753 1781 and 1902 refer to nonamers

(1380 and 1438 Aring2) hexamer (1132 Aring2) heptamer (1249 Aring2) heptamers (1500 and 1574 Aring2)

and nonamers (1543 and 1594 Aring2) respectively

S34

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 35: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

Table S8 Collision cross section for heteroligomers of Aβ11-22 incubated with PGG at the

molar ratio of 11

mz n

Aβ11-22

m

PGG

z

charge

Cross sectiona σexp

Isotropic

modelab

σiso

Ratio experiment

isotropicc

Ɛ(nm)

Isotropic Aβ11-

22ad

σiso(n)

Corrected Aβ11-22

ae

σcorr(nm)

808 1 1 +3 510 416 1225205 301 369

836 5 1 +10 975 952 1023979 880 901

836 5 1 +10 1098 952 1153158 880 1015

1033 5 2 +9 1040 1022 1018035 880 896

1033 5 2 +9 1132 1022 1108092 880 975

1079 3 1 +5 716 710 1007797 626 631

1212 1 1 +2 431 416 1035418 301 312

1212 1 1 +2 494 416 1186767 301 357

1303 2 1 +3 580 573 1012283 478 484

1430 9 1 +10 1380 1362 1013150 1302 1319

1430 9 1 +10 1438 1362 1055732 1302 1375

1541 6 2 +7 1132 1128 1003737 994 998

1683 1 2 +2 543 517 1049829 301 316

1683 1 2 +2 640 517 1237368 301 372

1753 7 2 +7 1249 1229 1016103 1101 1119

1781 7 6 +9 1500 1467 1022620 1101 1126

1781 7 6 +9 1574 1467 1073069 1101 1182

1902 9 4 +9 1543 1534 1005865 1302 1310

1902 9 4 +9 1594 1534 1039112 1302 1353

a values in Aring2

b isotropic cross section is calculated as σiso(nm) = [n σAβ11-22mon32 + m σPGGmon

32]23

where n and m are the number of Aβ11-22 and PGG molecules respectively and σAβ11-22mon

S35

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 36: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

(301 Aring2) and σPGGmon (220 Aring2) are the collision cross sections of the compact Aβ11-22 monomer

and 12346-penta-O-galloyl-β-D-glucopyranose (PGG) respectively The value of the

collision cross section of PGG (220 Aring2) was obtained from averaging the cross sections of

geometry-optimized PGG obtained from the TJ10 11 and PSA12 13 methods

c given by Ɛ(nm) = σexp σiso(nm)

d given by σiso(n) = σAβ11-22mon n23

e given by σcorr(nm) = σiso(n) Ɛ(nm) = σiso(n) [σexp σiso(nm)]

S36

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

S37

Page 37: ars.els-cdn.com · Web view11-22 (EVHHQKLVFFAE) peptides with free termini were purchased from GenScrip USA Inc. (Piscataway, NJ) and their samples prepared in submicron filtered

References

1 A Lomakin DS Chung GB Benedek DA Kirschner DB and Teplow D B On the nucleation and growth of amyloid beta-protein fibrils Detection of nuclei and quantitation of rate constants Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 1125-1129

2 T Wyttenbach PR Kemper MT Bowers Design of a new electrospray ion mobility mass spectrometer International Journal of Mass Spectrometry 212 (2001) 13-23

3 EA Mason EW McDaniel Transport Properties of Ions in Gases (1988) Wiley4 J Gidden A Ferzoco ES Baker MT Bowers Duplex formation and the onset of

helicity in poly d(CG)(n) oligonucleotides in a solvent-free environment Journal of the American Chemical Society 126 (2004) 15132-15140

5 DA Case T Darden TE Cheatham C Simmerling J Wang RE Duke R Luo RC Walker W Zhang KM Merz BP Roberts S Hayik A Roitberg G Seabra J Swails AW Goumltz I Kolossvaacutery KF Wong F Paesani J Vanicek RM Wolf J Liu X Wu SR Brozell T Steinbrecher H Gohlke Q Cai X Ye J Wang M-J Hsieh G Cui DR Roe DH Mathews MG Seetin R Salomon-Ferrer C Sagui V Babin T Luchko S Gusarov A Kovalenko PA Kollman (2012) AMBER 12 University of California San Francisco

6 FY Dupradeau A Pigache T Zaffran C Savineau R Lelong N Grivel D Lelong W Rosanski P Cieplak The RED tools advances in RESP and ESP charge derivation and force field library building Physical Chemestry Chemical Physics 12 (2010) 7821-7839

7 E Vanquelef S Simon G Marquant E Garcia G Klimerak JC Delepine P Cieplak FY Dupradeau RED Server a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments Nucleic Acids Research 39 (2011) W511-517

8 NEC de Almeida T D Do M Tro NE LaPointe SC Feinstein J-E Shea MT Bowers Opposing effects of cucurbit[7]uril and 12346-penta-O-galloyl-β-d-glucopyranose on amyloid β25-35 assembly ACS Chemical Neuroscience 7 (2016) 218-226

9 WL Jorgensen J Chandrasekhar JD Madura RW Impey ML Klein Comparison of simple potential functions for simulating liquid water Journal of Chemical Physics 79 (1983) 926-935

10 AA Shvartsburg MF Jarrold An exact hard-spheres scattering model for the mobilities of polyatomic ions Chemical Physics Letters 261 (1996) 86-91

11 MF Mesleh JM Hunter AA Shvartsburg GC Schatz MF Jarrold Structural information from ion mobility measurements Effects of the long-range potential Journal of Physical Chemistry 100 (1996) 16082-16086

12 C Bleiholder S Contreras TD Do MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II) Model parameterization and definition of empirical shape factors for proteins International Journal of Mass Spectrometry 345 (2013) 89-96

13 C Bleiholder T Wyttenbach MT Bowers A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I) Method International Journal of Mass Spectrometry 308 (2011) 1-10

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Termini di versamento di TEPAI · 2019. 5. 9. · della legge 4256/2014 Imbarcazioni professionali da diporto, noleggiate per intero, ai sensi della legge 4256/2014 (Gazzetta Ufficiale

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Colloidal submicron-palladium particles stabilized with ...Palladium particles were synthesized as follows. 100 cm3 ethanol solution including 20 mg palladium acetate was mixed with

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ACT 50-75-95 l...UNI EN ISO ±0.05 ±0.5 22768/2-k oltre 4000 Toll. lineari Quote lineari fino a UNI EN ISO 22768/1-f Peso[kg]:264,32 Proprieta' riservata a termini di legge.Vietata

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