Structure, orientation and affinity for interfaces and lipids of ideally amphipathic lytic LiKj(i=2j) peptides

The behavior of lytic ideally amphipathic peptides of generic composition L iKj(i = 2j) and named LKn, n=i+j, is investigated in situ by the monolayer technique combined with the recently developed polarization modulation IR s pectroscopy (PMIRRAS). A change in the secondary structure occurs versus pe ptide length. Peptides longer than 12 residues fold into alpha-helices at i nterfaces as expected from their design, while enough shorter peptides, fro m 9 down to 5 residues, form intermolecular antiparallel beta-sheets. Analy sis of experimental and calculated PMIRRAS spectra in the amide I and II re gions show that peptides are flat oriented at the interfaces. Structures an d orientation are preserved whatever the nature of the interface, air/water or DMPC monolayer, and the lateral pressure. Peptide partition constants, K-aff(Pi), are estimated from isobar surface increases of DMPC monolayers. They strongly increase when Pi decreases from 30 mN/m to 8 mN/m and they va ry with peptide length with an optimum for 12 residues. This non-monotonous dependence fits with data obtained in bilayers and follows the hemolytic a ctivity of the peptides. Lipid perturbations due to peptide insertion essen tially detected on the PO4- and CO bands indicate disorder of the lipid hea d groups. Lysis induced on membranes by such peptides is proposed to first result from their flat asymmetric insertion. (C) 1999 Elsevier Science B.V. All rights reserved.