RELEASE OF AQUEOUS CONTENTS FROM PHOSPHOLIPID-VESICLES INDUCED BY CECROPIN-A (1-8) MAGAININ-2 (1-12) HYBRID AND ITS ANALOGS

The membrane-disrupting properties of cecropin A (1-8)-magainin Z (1-1 2) hybrid peptide, which has higher antitumor with less hemolytic acti vities than cecropin A (1-8)melittin (1-12), and its analogues were as sessed by measuring the induced release of vesicle-entrapped fluoresce nce probes. A model membrane was made of zwitterionic phospholipid (ph osphatidylcholine) or the mixture of negatively and zwitterionic phosp holipids (phosphatidylcholine and phosphatidylserine). The extent of l eakage of the aqueous content of the phospholipid vesicles was found t o have remarkable discrepancies according to the amphipathic nature of each analogue peptide. The entrapped high molecular weight solute (fl uorescein-labeled immunoglobulin G, 55 kDa) also was released by the a nalogue which had the largest hydrophobic region and the highest amphi pathic score among peptides tested. As the result of the determination of the relationships between the membrane-disrupting properties and t he hydrophobicity values of peptides, it was found that the membrane-d isrupting activity increased according to increasing the hydrophobicit y of the peptide. The tryptophan fluorescence emission spectra and CD spectra showed that on interaction with the phospholipid vesicle, the peptide acquired the ordered structure and ct-helical conformation by moving a tryptophan residue into the nonpolar environment of the phosp holipid vesicle. These results suggest that the breakdown of the lipid bilayer was mediated by the alpha-helical amphipathic structure of th e peptide interacting with the lipid bilayers as well as the by the hy drophobicity of the peptide.