Potential Therapeutic Applications of Magainins and other Antimicrobial Agents of Animal Origin

  1. Joan Marsh Organizer and
  2. Jamie A. Goode
  1. Leonard Jacob and
  2. Michael Zasloff

Published Online: 28 SEP 2007

DOI: 10.1002/9780470514658.ch12

Ciba Foundation Symposium 186 - Antimicrobial Peptides

Ciba Foundation Symposium 186 - Antimicrobial Peptides

How to Cite

Jacob, L. and Zasloff, M. (2007) Potential Therapeutic Applications of Magainins and other Antimicrobial Agents of Animal Origin, in Ciba Foundation Symposium 186 - Antimicrobial Peptides (eds J. Marsh and J. A. Goode), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470514658.ch12

Author Information

  1. Magainin Pharmaceuticals Inc., 5110 Campus Drive, Plymouth Meeting, PA 19462, USA

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471950257

Online ISBN: 9780470514658

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Keywords:

  • magainins;
  • antimicrobial agents;
  • bacteria;
  • escherichia coli;
  • protozoa

Summary

Magainins are a family of linear, amphipathic, cationic antimicrobial peptides, 21 to 27 residues in length, found in the skin of Xenopus laevis. They kill microbial targets through disruption of membrane permeability. They exhibit selectivity, on the basis of their affinity for membranes which contain accessible acidic phospholipids, a property characterizing the cytoplasmic membranes of many species of bacteria. Magainins are broad-spectrum antimicrobial agents exhibiting cidal activity against Gram-negative and Gram-positive bacteria, fungi and protozoa. In addition these peptides lyse many types of murine and human cancer cells at concentrations 5–10-fold lower than normal human cells. Because of their selectivity, broad spectrum, low degree of bacterial resistance and ease of chemical synthesis, magainins are being developed as human therapeutic agents. The most advanced candidate is MSI-78, a 22-residue magainin analogue. This peptide is currently in human Phase IIb/III clinical trials in studies intended to evaluate its efficacy as a topical agent for the treatment of impetigo. Preclinical studies have demonstrated that analogues of magainin exhibit activity in vivo against malignant melanoma and ovarian cancer cells in mouse models. Intravenous administration of several magainin analogues has been shown to treat effectively systemic Escherichia coli infections in the mouse.