MODULATION OF MEMBRANE-ACTIVITY OF AMPHIPATHIC, ANTIBACTERIAL PEPTIDES BY SLIGHT MODIFICATIONS OF THE HYDROPHOBIC MOMENT

Starting from the sequences of magainin 2 analogs, peptides with sligh tly increased hydrophobic moment (mu) but retained other structural pa rameters were designed. Circular dichroism investigations revealed tha t all peptides adopt an alpha-helical conformation when bound to phosp holipid vesicles, Analogs with increased mu were considerably more act ive in permeabilizing vesicles mainly composed of zwitterionic lipid, In addition, the antibacterial and hemolytic activities of these analo gs were enhanced. Correlation of permeabilization and binding indicate d that the activity increase is predominantly caused by an increased m embrane affinity of the peptides due to strengthened hydrophobic inter actions. (C) 1997 Federation of European Biochemical Societies.