Modifications of Hydrophobic Value and Hydrophobic Moment Value of Cationic Model Peptides for Conversion of Peptide-Membrane Interactions
The hydrophobic value <<I>H</I>> and hydrophobic moment value <μ> of helical peptides correlate with membrane–peptide interactions such as ion channel forming or membrane perturbation. In this paper, two cationic amphiphilic peptides, ALSAALKAALSWASLAAKLAASLA-amide (Ap) and KK-ALSAALKAALSWASLAAKLAASLA-KK-amide (KAp), consisting of 24 and 28 amino acid residues, respectively, were synthesized to acquire antimicrobial activities and to reduce the high hemolytic activity of cationic helical peptide, LARLLARLLARLLRALLRALLRAL-amide (4<SUB>6</SUB>), reported previously. Both peptides were designed to possess higher hydrophobic values and lower hydrophobic moment values than those of 4<SUB>6</SUB>. Circular dichroism (CD) measurements of the peptides showed that the peptides had lower α-helical content than that of 4<SUB>6</SUB> in aqueous solutions as well as the membrane mimetic environments. 4<SUB>6</SUB> did not show any antibacterial activity whereas KAp and Ap had antibacterial activities against Gram-positive and -negative bacteria. In contrast, the hemolytic activities of Ap and KAp decreased to less than that of 4<SUB>6</SUB>. Electrophysiological experiments were carried out to compare ion channel formation. Both peptides showed ion conductance patterns distinguishable from the patterns of 4<SUB>6</SUB> and pore forming with flexible structures was suggested. In addition, the flanking cationic residues of KAp tended to increase the channel opening durations.
- Bulletin of the Chemical Society of Japan
Bulletin of the Chemical Society of Japan 81(6), 733-739, 2008-06-15
The Chemical Society of Japan