| Abstract: | Analogs of the cationic C‐terminal segments of human‐β‐defensins HBD1‐3, Phd1‐3 with a single disulfide bond, exhibited comparable antimicrobial activity that was salt sensitive. They did not show hemolytic activity. In this study, N‐terminal myristoylation was carried out on Phd1‐3 to examine whether increasing hydrophobicity would result in improved antibacterial activity. The antibacterial activity of the oxidized myristoylated peptides MPhd1‐3 and their reduced forms MPhd1r‐3r was determined. These peptides showed enhanced antibacterial activity as compared to Phd1‐3, on mid‐log phase and stationary phase of Staphylococcus aureus and Escherichia coli, except MPhd1r‐3r that were inactive on stationary‐phase E. coli. In the presence of 150 mm NaCl, MPhd1‐3 showed activity against S. aureus. MPhd1and two exhibited activity against E. coli but MPhd3 was inactive. Zeta potential measurements indicated that MPhd1‐3 were more effective in surface charge neutralization of bacteria as compared to Phd1‐3. MPhd1‐3 exhibited hemolytic activity to varying extents with MPhd1 being most hemolytic. The data indicate that myristoylation enhances antibacterial activity and modulates hemolytic activity to different extents. Apart from hydrophobicity, distribution of cationic residues in MPhd1‐3 plays important roles for these activities. |
