脂質膜とペプチドとの相互作用に関する分子論的考察

Abstract

We have investigated the interactions of three classes of antimicrobial peptides (hypelcin A, trichopolyn I, and magainins) with lipid bilayers by using several physichochemical techniques (fluorescence, circular dichroism, infrared absorption, and differential scanning calorimetry) to obtain basic information on the molecular-level mechanisms for their bioactivities. In zwitterionic phosphatidyl-choline membranes, hydrophobic peptides, hypelcin A and trichopolyn I, form helices, deeply penetrating the hydrophobic region of the bilayers. There are no specific interactions between membranebound peptide molecules. The penetration disrupts the lipid packing, permeabilizing the bilayers. The membrane action of hypelcin A, the larger peptide, is three fold stronger. In contrast to these hydrophobic peptides, cationic magainin peptides specifically bind with acidic lipid bilayers, e.g., phosphatidylglycerol, to form amphiphilic helices. Electrostatic interactions are important in the binding process. The helical rods lie parallel to the membrane surface and form an aggregate. Magainins cause minimal perturbation of the hydrophobic core of the membranes, coinciding with much weaker membrane permeabilization activity. However, detailed permeabilization mechanisms are a subject of further study.