Mode of action of linear amphipathic alpha-helical antimicrobial peptides

Biopolymers. 1998;47(6):451-63. doi: 10.1002/(SICI)1097-0282(1998)47:6<451::AID-BIP4>3.0.CO;2-F.

Abstract

The increasing resistance of bacteria to conventional antibiotics resulted in a strong effort to develop antimicrobial compounds with new mechanisms of action. Antimicrobial peptides seem to be a promising solution to this problem. Many studies aimed at understanding their mode of action were described in the past few years. The most studied group includes the linear, mostly alpha-helical peptides. Although the exact mechanism by which they kill bacteria is not clearly understood, it has been shown that peptide-lipid interactions leading to membrane permeation play a role in their activity. Membrane permeation by amphipathic alpha-helical peptides can proceed via either one of the two mechanisms: (a) transmembrane pore formation via a "barrel-stave" mechanism; and (b) membrane destruction/solubilization via a "carpet-like" mechanism. The purpose of this review is to summarize recent studies aimed at understanding the mode of action of linear alpha-helical antimicrobial peptides. This review, which is focused on magainins, cecropins, and dermaseptins as representatives of the amphipathic alpha-helical antimicrobial peptides, supports the carpet-like rather the barrel-stave mechanism. That these peptides vary with regard to their length, amino acid composition, and next positive charge, but act via a common mechanism, may imply that other linear antimicrobial peptides that share the same properties also share the same mechanism.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Linear Models
  • Molecular Sequence Data
  • Peptides*
  • Protein Structure, Secondary*
  • Solubility
  • Water / chemistry

Substances

  • Anti-Bacterial Agents
  • Peptides
  • Water