N-TERMINAL AND C-TERMINAL EFFECT OF AMPHIPHILIC ALPHA-HELICAL PEPTIDES ON THE INTERACTION WITH MODEL-MEMBRANE AND BIO-MEMBRANE

We previously designed and synthesized five N- and C-termini-free amph iphilic alpha-helical model peptides (Hel series) with a systematicall y varied hydrophobic-hydrophilic balance (HHB) that showed hemolytic a ctivity, but no antimicrobial activity. However, an N-acetylated and C -amidated model peptide, peptide 3 [S. E. Blondelle and R. A. Houghten , Biochemistry, 31, 12688 (1992)], similar to a Hel series peptide, He l 9-9, whose hydrophobic and hydrophilic amino acid residues and areas are equal in the alpha-helical structure, have exhibited both hemolyt ic and antimicrobial activities. Thus, to investigate the N- and C-ter minal effect of the Hel series peptides on their antimicrobial activit y, we designed and synthesized three peptides (Cap-Bel series), both t ermini-blocked by N-acetyl and C-amide groups. Their interaction mode with membranes was examined through reverse-phase high-performance liq uid chromatography and circular dichroism spectroscopy as well as meas urements of the hemolytic activity, antimicrobial activity, and membra ne-clearing ability. No essential difference was found in either the t erminal-free or -protected peptides, indicating that acetylation of th e N-terminal and amidation of C-terminal did not affect their intrinsi c antimicrobial activity in spite of a considerable change in the bind ing properties to lipids and hemolytic activities.