Antimicrobial Peptides

Sebastian Groß01.07.2015

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Antimicrobial Peptides

Peptide-based small molecules

2 to 150 amino acids

Evolutionary conserved

Plants

Insects

Vertebrates

Bacteria

Innate immunity

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What is interesting about AMPs?

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Loops or β-hairpin β-sheets

α-helical extended

AMP structure

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Mechanism of cell death by AMPs

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Mode of action

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The oral cavity – a source of AMPs?

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The oral cavity – a source of AMPs?

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α- and β-defensins

β-defensins specific in mammalian epithelial cells

33 to 47 amino acids

β-sheet AMPs

Three intramolecular disulfide bonds

Predominantly cationic and hydrophobic

Bind LPS in bacterial cell membranes

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Histatins

Exclusively in humans and higher primats

Extended AMPs

7 to 38 amino acids

Histidine-rich and cationic

Encoded by two genes (HTN1 and HTN3)

Inhibition of bacterial proteases

Fungistatic effect (C. albicans)

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AMP synthesis

Biological synthesis

In vivo

In vitro

Chemical synthesis

Liquid-phase synthesis

Solid-phase peptide synthesis

recombinant systems

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In-vivo biological synthesis

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In-vitro biological synthesis

mRNA

Ribosome

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Chemical synthesis

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Semi-synthesis

Combined biological and chemical synthesis

Avoiding inefficient coupling steps

Avoiding poor handling properties

Further chemical modifications after biological synthesis

Enables use of non-proteinogenic amino acids

Sometimes better reaction yields

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Pros Cons

High degree of specificity Proteolytic degradation

Generally low toxicity Widely unknown mode of action

Easy metabolization

Chemical modifications Loss of efficacy during storage

Formulation techniques

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Conclusion

AMPs are promising drug candidates to treat a variety of

diseases in the future

The mode of action is widely unknown

Chemical modifications and formulation techniques can

improve AMP efficacy