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Antimicrobial Peptides

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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 ... – PowerPoint PPT presentation

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Title: Antimicrobial Peptides


1
Antimicrobial Peptides
  • An ancient immune system?
  • or

2
This frog could save your leg
3
Antimicrobial peptidesWhere 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

4
Antimicrobial peptidesWhat are they?
  • 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

5
Defensin-like
HUMAN PLANT
6
Helical PGLa(frog)
7
Antimicrobial peptidesWhat are they?
  • Small Proteins
  • lysozyme
  • phospholipase a
  • cathepsins

8
Antimicrobial peptidesWhat do they do?
  • Antifungal
  • Antibacterial
  • Gram positive
  • Gram negative

cell wall
membrane
LPS
OM
cell wall
membrane
9
Antimicrobial peptidesWhat do they do?
  • 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?

10
Antimicrobial peptidesWhy are they picky?
  • 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!

11
Antimicrobial peptidesHow are they made?
  • NF?B-type genetic element seems universal
  • like acute phase response in humans
  • Protective anionic piece is common,

signal
propiece
mature
12
Mechanisms?
13
Antimicrobial peptidesNew Clinical Antibiotics?
  • 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

14
Antimicrobial peptidesProblems with use?
  • Proteolysis, Salt, Transport properties
  • Manufacture
  • chemical synthesis is very expensive100s/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)
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