Indolicidin-derived antimicrobial peptide analogs with greater bacterial selectivity and requirements for antibacterial and hemolytic activities

Abstract

Indolicidin (ILPWKWPWWPWRR-NH2) has received attention due to its unique primary structure and biological activities. In this study, amide bonds at various positions in indolicidin were replaced with the reduced amide bonds ψ[CH2NH] and the effect of the secondary structure on the biological activity was investigated. The circular dichroism spectra revealed that the rigidity and hydrogen bond of the amide bond between Trp8 and Trp9 were important for stabilizing the turn structure of indolicidin. A structure–activity study revealed that the turn structure of indolicidin was not required for antimicrobial activity and leakage activity for LUVs with a negatively charged surface. The pseudopeptide containing two reduced amide bonds showed less hemolytic activity as well as improved stability without a decrease in its antimicrobial activity. These results will provide valuable information for designing indolicidin analogs with greater bacterial selectivity and increased stability and for elucidating the role of the secondary structure of membrane-active peptides for antimicrobial and hemolytic activities.