1. Antimicrobial Peptides Sebastian Groß 01.07.2015

2. Antimicrobial Peptides  Peptide-based small molecules  2 to 150 amino acids  Evolutionary conserved  Plants  Insects  Vertebrates  Bacteria  Innate immunity 2

3. 3 What is interesting about AMPs?

4. 4 Loops or β-hairpinβ-sheets α-helicalextended AMP structure

5. Mechanism of cell death by AMPs 5

6. 6 Mode of action

7. 7

8. 8 The oral cavity – a source of AMPs?

9. 9

10. 10 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

11. 11 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)

12. 12

13. 13 AMP synthesis  Biological synthesis  In vivo  In vitro  Chemical synthesis  Liquid-phase synthesis  Solid-phase peptide synthesis recombinant systems

14. 14 In-vivo biological synthesis

15. 15 In-vitro biological synthesis mRNA Ribosome

16. 16 Chemical synthesis

17. 17 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

18. 18 ProsCons High degree of specificityProteolytic degradation Generally low toxicityWidely unknown mode of action Easy metabolization Chemical modificationsLoss of efficacy during storage Formulation techniques

19. 19 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

21. SA Baltzer, MH Brown (2011) Antimicrobial Peptides – Promising Alternatives to Conventional Antibiotics. J Mol Microbiol Biotechnol; 20:228 – 235. CL Bevins, NH Salzman (2011) Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nature Microbiol; 356 – 368. JP da Costa, M Cova, R Ferreira, R Vitorino (2015) Antimicrobial peptides: an alternative for innovative medicines? Appl Microbiol Biotechnol; 99:2023 - 2040. G Wang (2014) Human Antimicrobial Peptides and Proteins. Pharmaceuticals; 7, 545 – 594. https://www.lifetechnologies.com/de/de/home/life-science/protein-biology/protein- biology-learning-center/protein-biology-resource-library/pierce-protein- methods/peptide-synthesis.html (22.06.2015)

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