Antimicrobial Peptides - University of Wisconsin–Eau ….pptVIP

Antimicrobial Peptides An ancient immune system? or This frog could save your leg Antimicrobial peptides:Where are they? In everything from Amoebas to Humans Abundant in vertebrates in: External Mucosa eyes, mouth, genitourinary, skin, lung, trachea Immune cells neutrophils Intestinal tract (duodenum) in humans; Paneth cells are the source Cationic, Amphipathic Linear ?-helical (20-35 AA) Magainin, cecropins, histatin Pro-Arg rich (more polar) bac 5 and 7 (30-50 AA; 70% pro/arg) Disulfide Rich ?-structure amoebapores, NK-lysin Disulfide Rich ?-structure Defensins: three or more disulfide (30-70 AA) “Loops” (11-22 AA) tachpyylesins, protegrins ,ranalexin, polymyxin Small Proteins lysozyme phospholipase a cathepsins Antifungal Antibacterial Gram positive Gram negative Permeabilize OM, IM channels lysis D-analogs sometimes as effective Carry LPS immune stimulation? Enzyme action cell wall destruction lipase , protease synergistic w/cationic peptides? Bacteria have : more negative charge recall: peptides are cationic no sterols, little phosphatidylcholine or SM a lot of PG/PE/cardiolipin/PS some tumor cells too! NF?B-type genetic element seems universal like acute phase response in humans Protective anionic piece is common, Indolicidin analog fights test infections IP or IV Protegrin analog helps chemotherapy oral mucositis Magainin analog, LOCILEX? Cream underwent clinical trials (now Genaera Corporation ) diabetic ulcers, not approved Squalamine, amino sterol cationic peptide analog-anti-obesity and anti angiogenesis Proteolysis, Salt, Transport properties Manufacture chemical synthesis is very expensive;$100’s/gram! organic mimics or modular design may help May be possible to produce in bacteria or plants protective piece for bacteria TMV with tobacco (GENEWARE?) Antimicrobial peptides:What are they? HUMAN PLANT Defensin-like Helical: PGLa(frog) Antimicrobial peptides:What are they? Antimicrobial peptides:What do they do? cell wall cell wall