Π- Stacking Interaction Ana Gabriela Murguía Carlos Villa
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- Stacking Interaction Ana Gabriela MurguaCarlos Villa
- Stacking InteractionProtenas no homologasDifraccin de Rayos XPosicin preferida y orientacin de interacciones no covalentesAminocidos Aromticos (Cad. Laterales)Dimeros
- Stacking InteractionAgentes medicinales contienen sustituyentes aromticosEl reconocimiento diferencial esta basado en las interacciones aromticas
EstructurasOff centered parallel displaced (1p)T-Shaped (1t)
HiptesisEn el core de la protena (Hidrofobico) en el estado slido, las propiedades dinmicas de la interaccin benceno-benceno estn satisfechas y una estructura preferida prevalece, aunqueDmero de Benceno
Materiales y MtodosDeterminacin del CentroideDistancia ms cercana de contacto
Esta combinacin de datos corresponde a Off centered parallel configuration
La forma de la distribucin Y puede ser extrapolada a una distribucin de Boltzman, bajo ciertas asunciones
ResultadosLa estructura paralela descolocada es mas estable que la estructura con forma TLa diferencia de la energia es dependiente del seno yLa tempertura es 300K
DiscusinLa estructura paralela descolocada es mas estable que una estructura de forma T en 0.5 0.75 kcal/molPhe-Phe en 1.0 kcal/molOtros autores dicen lo contrario (adems que no existen en protenas) Quizs debido a descuido en la distribucin de los ngulos
Aromatic Interaction- interaction is a noncovalent interaction between organic compounds containing aromatic moieties. - interactions are caused by intermolecular overlapping of p-orbitals in -conjugated systems, so they become stronger as the number of -electrons increases.
The role of -stacking in self-assembly processesMany areas of chemistry and biochemistry, most notably in molecular recognition and self-assembly.Aromatic rings tend to form high-order clusters of four different types: parallel displaced, Tshaped,parallel staggered, or Herringbone.
Alzheimers disease (AD)Diabetes mellitus (type II)Prion diseases Familial amyloidosis Light chain amyloidosis Formation is a process in which normal well-folded cellular proteins undergo a self-assembly process that leads to the formation of large and ordered protein structures.
Aromatic residues in short amyloid related peptide
Islet amyloid polypeptide
Minimal amyloid-forming fragment of the 37 amino acid islet amyloid polypeptide (IAPP), or amylin. IAPP deposits found postmortem in 95% diabetes.Peptide form amyloid fibers in vitro. 6 residue peptide fragment of human IAPP (NFGAIL) form amyloid fibrils similar to the full-length protein. 5 residue fragment (FGAIL) forms ordered amyloid fibrils, are different in morphology from the full-length peptide.A shorter peptide corresponding to the GAIL sequence did not form any fibrils at all.
Brain senile amyloid plaques composed of the AB peptideShort fragment of AB contains 2 phenylalanine residues (QKLVFF) was shown to bind specifically to full-length peptide. The short peptide could inhibit amyloid formation by the full-length AB polypeptide. LVFFA and its derivatives and LPFFD KLVFFAE, forms amyloid fibrils.
Amyloid fibrils process of Molecular recognition and self-assembly, the high affinity and selectivity of the FF motif seems to provide the molecular recognition.
Aortic medial amyloid
Aromatic residues is the octapeptide fragment (NFGSVQFV) of the 364 amino acid lactadherin protein.Amino acid sequence analysis of the 5.5 kDa peptide demonstrated that derived from an integral proteolytic fragment of lactadherin.Was synthesized and characterized form amyloid deposits
Animal and yeast prions
Animal prion diseases are sporadic or inherited neurodegenerative disorders that are transmitted by a protein infective agent. The agent is a misfolded form (PrS) of a normal cell protein (PrP) that acts by a conversion of normal folded PrP proteins to amyloid-like aggregates. The importance of the octapeptide repeats is the fact result from the insertion of one to nine extra octapeptide repeats in addition to the five repeats that occur in the normal prion protein.A misfolded variant in yeast (Sup35p) of a normal cellular protein (Sup35), which has been shown to cause a change in the phenotype of a normal cell by converting the normal protein into aggregates.
The role of -stacking interactions in chemistry
Amyloid fibril formation is basically a process of intermolecular recognition and self-assembly, the -stacking can provide: 1) an energetic contribution that stems from the stacking itself; such a contribution can thermodynamically drive the self-assembly process,2) specific directionality and orientation provided by the specific pattern of stacking.
Cont The mechanism of amyloid includes a stepwise assembly of short recognition elements. At the first stage, 2 structural elements that contain aromatic residues form a bimolecular structure, which is restricted by the allowed geometry of - stacking. Followed by a stepwise addition of further monomers containing the same recognition elements. Again, the overall structural organization of the addition process is being directed by the restricted geometries of the stacking interaction.