Interaction of α-helical peptides with phospholipid membrane: effects of chain length and hydrophobicity of peptides

To investigate the interaction of amphiphilic α-helical peptides with phospholipid membranes, we synthesized Ac-(Leu-Ala-Arg-Leu)3-NHcH3 (43) and three derivatives, in which the chain length and the size of the hydrophobic region of the peptides were different from each other. These peptides formed an α-helical structure in the presence of vesicles. In the membrane-perturbation measurement, only 43 showed a strong membrane-perturbation activity below phase-transition temperature (25°C), but above phase-transition temperature (50°C), most peptides showed similar strong activities. On the other hand, in membrane-fusion measurement the long peptides, e.g., Ac-(Leu-Ala-Arg-Leu)3-(Leu-Arg-Ala-Leu)3-NHCH3, had strong activities at low peptide concentrations at 25°C. The present study indicated a parallel relationship did not always exist between membrane fusion and perturbation caused by peptides.