SELECTIVE INTERACTION OF SYNTHETIC ANTIMICROBIAL PEPTIDES DERIVED FROM SAPECIN-B WITH LIPID BILAYERS

By measuring carboxyfluorescein leakage from liposomes and the increas e in membrane current through planar lipid bilayer membranes, we exami ned the capacities of a series of low-molecular-weight cationic amphip hilic peptides derived from the alpha-helix domain of sapecin B for me mbrane-perturbation and ion-channel formation. Some of these peptides strongly interact with membranes containing acidic phospholipids and p hosphatidylethanolamine, with a very negative potential, which are cha racteristic of the Escherichia coli membrane, in parallel with their a ntimicrobial activity. In contrast, they do not interact with membrane s which predominantly contain choline phospholipids and cholesterol in their outer leaflets, with a slightly negative potential, all of whic h are characteristic of eukaryotic membranes, thereby providing a mole cular basis for their selective toxicity. Membranes doped with these p eptides are as permeable to inorganic phosphates as to chloride ions a nd are far more permeable to cations. The loss of inorganic phosphates may damage bacterial cells due to rapid depletion of cytoplasmic ATP, Examination of the structure-activity relationships of a series of de rived peptides in their interaction with a model of the E. coli membra ne confirmed the necessity of cationic amphiphilicity for the peptides to attack the bacterial membrane and to exhibit antimicrobial activit y.