N- and C-Terminal Effect of Amphiphilic α-Helical Peptides on the Interaction with Model- and Bio-Membranes

We previously designed and synthesized five N- and C-termini-free amphiphilic α-helical model peptides (Hel series) with a systematically varied hydrophobic–hydrophilic balance (HHB) that showed hemolytic activity, 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, Hel 9-9, whose hydrophobic and hydrophilic amino acid residues and areas are equal in the α-helical structure, have exhibited both hemolytic and antimicrobial activities. Thus, to investigate the N- and C-terminal effect of the Hel series peptides on their antimicrobial activity, we designed and synthesized three peptides (Cap-Hel series), both termini-blocked by N-acetyl and C-amide groups. Their interaction mode with membranes was examined through reverse-phase high-performance liquid chromatography and circular dichroism spectroscopy as well as measurements of the hemolytic activity, antimicrobial activity, and membrane-clearing ability. No essential difference was found in either the terminal-free or -protected peptides, indicating that acetylation of the N-terminal and amidation of C-terminal did not affect their intrinsic antimicrobial activity in spite of a considerable change in the binding properties to lipids and hemolytic activities.