Biol. Pharm. Bull. 28(1) 148—150 (2005)

naturally-occurring antimicrobial peptides provide a valuable tool for studying the role of different structural features in the activity of those peptides. A large array of derivatives based upon these structural models has been synthesized and studied in an attempt to increase the potency and selectivity of the native antimicrobial peptides. Enhancing the antimicrobial potency is often accompanied by a concomitant reduction in selectivity between bacterial and mammalian cells. The affinity of antimicrobial peptides for the membrane surface may be a crucial factor in the lytic process, since selective binding to different phospholipids is central to the design of antimicrobial peptides that can discriminate between bacterial and mammalian cells. We recently designed a novel linear cationic 18-residue peptide, (KIGAKI)3-NH2, which has the potential to form an amphipathic b-sheet structure when bound to a lipid bilayer. This model b-sheet peptide possessed potent antimicrobial activity and low hemolytic activity. In a previous study, we developed analogues of KIGAKI containing a single tryptophan residue at position 2 (W2-KIGAKI), position 8 (W8-KIGAKI), or position 18 (W18-KIGAKI), respectively, in each case replacing an isoleucine residue. In addition, an octanoylated analogue of W8-KIGAKI (Oct-W8-KIGAKI) was included since the inclusion of an alkyl group at the N-terminus of the peptide can sometimes increase the antimicrobial potency. The lytic properties of these model tryptophancontaining peptides were compared by monitoring peptideinduced permeability changes in liposomes with varying lipid composition. The use of surface plasmon resonance (SPR)-based biosensors to study the membrane-binding properties of antimicrobial peptides has the advantage of not requiring the presence of labels or chromophores. We previously demonstrated the efficacy of SPR by monitoring the interactions of various peptides to the lipid membranes. We have shown that the kinetic rate constants and the affinity of membrane interactions measured using this technique can provide important insights into the mechanism of peptide–membrane interactions. In the present study, we used SPR to investigate the lipid membrane-binding properties of four b-sheet cationic tryptophan-containing peptides, W2-KIGAKI, W8KIGAKI, W18-KIGAKI, and Oct-W8-KIGAKI, in combination with four model lipid membrane systems. The results revealed significant differences in binding characteristics and kinetics among the peptides and correlated well with their lytic properties and bactericidal activity.