title: Mode of action of linear amphipathic alpha-helical antimicrobial peptides.
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.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Z
authors.initials: Z
authors.lastname: Oren
authors.forename: Y
authors.initials: Y
authors.lastname: Shai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D016014:Linear Models; D008969:Molecular Sequence Data; D010455:Peptides; D017433:Protein Structure, Secondary; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D014867:Water