Transcript Antimicrobial Peptides

Sebastian Groß
01.07.2015
Antimicrobial Peptides
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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AMP structure
Loops or β-hairpin
β-sheets
α-helical
extended
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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
recombinant systems
 In vitro
 Chemical synthesis
 Liquid-phase synthesis
 Solid-phase peptide synthesis
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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
Generally low toxicity
Proteolytic degradation
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
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