Conformational studies of amphipathic α-helical peptides containing an amino acid with a long alkyl chain and their anchoring to lipid bilayer liposomes

Abstract

In order to investigate the conformation and orientation of lipid-bound peptides and proteins in the lipid bilayer, basic amphipathic α-helical peptides with a long alkyl chain, palmitoyl-(Leu-Ala-Arg-Leu) 3-NHCH 3 (P-4 3) and Ac-Leu-Ala-Arg-Leu-Trp-Amy-Arg-Leu-Leu-Ala-Arg-Leu-NHCH 3 (Amy-4 3, Amy; α-aminomyristic acid) were designed and synthesized. The conformational features and spectroscopic behavior in a buffer solution and in neutral and acidic liposomes were studied by CD, dye-leakage, and fluorescence measurements. The CD data indicated that P-4 3 took an α-helical structure in aqueous solution and in neutral and acidic liposomes. On the other hand, Amy-4 3 took a β-structure in aqueous solution and an α-helical structure in neutral and acidic liposomes. The conformational change of Amy-4 3 was confirmed by fluorescence study on lipid titration of the peptide. The dye-leakage experiment showed that both peptides interacted with acidic liposomes to perturb them, but less effectively than Ac-(Leu-Ala-Arg-Leu) 3-NHCH 3 (4 3) which has no long alkyl group. Based on these results, a discussion is made concerning the conformation and orientation of peptides in aqueous solution and in the lipid bilayer.