INTERACTION OF INDOLICIDIN, A 13-RESIDUE PEPTIDE RICH IN TRYPTOPHAN AND PROLINE AND ITS ANALOGS WITH MODEL MEMBRANES

Indolicidin is a 13-residue broad-spectrum antibacterial peptide isola ted from bovine neutrophils. The primary structure of the peptide ILPW KWPWWPWRR-amide (IL) reveals an un usually high percentage of tryptoph an residues. IL and its analogues where proline residues have been rep laced by alanine (ILA) and trp replaced by phe (ILF) show comparable a ntibacterial activities. While IL and ILA are haemolytic, ILF does not have this property. Since aromatic residues would strongly favour par titioning of the peptide into the lipid bilayer interface, the biologi cal activities of IL and its analogues could conceivably arise due per turbation of the lipid bilayer of membranes. We have therefore investi gated the interaction of IL and its analogues with lipid vesicles. Pep tides IL and ILA bind to lipid vesicles composed of phosphatidylcholin e and phosphatidylethanol amine:phosphatidyl glycerol: cardiolipin. Th e position of lambda(max) and I- quenching experiments suggest that th e trp residues are localized at the membrane interface and not associa ted with the hydrophobic core of the lipid bilayer in both the peptide s. Hence, membrane permeabilization is likely to occur due to deformat ion of the membrane surface rather than formation of transmembrane cha nnels by indolicidin and its analogues. Peptides ILA, IL and ILF cause the release of entrapped carboxyfluorescein from phosphatidyl choline vesicles. The peptide-lipid ratios indicate that ILF is less effectiv e than IL and ILA in permeabilizing lipid vesicles, correlating with t heir haemolytic activities.