Indolicidin analogs with broad-spectrum antimicrobial activity and low hemolytic activity

Abstract

To create a broad-spectrum peptide biocide, we synthesized 45 analogs of antimicrobial peptide indolicidin (H-Ile-Leu-Pro-Trp-Lys-Trp-Pro-Trp-Trp-Pro-Trp-Arg-Arg-NH₂). Among them the peptides H-Ile-Leu-Pro-(2-Me)Phe-Lys-(2-Me)Phe-Pro-(2-Me)Phe-(2-Me)Phe-Pro-(2-Me)Phe-Arg-Arg-NH₂ and HN₂-(CH₂)₁₀-Ile-Leu-Pro-D-Phe-Lys-D-Phe-Pro-D-Phe-D-Phe-Pro-D-Phe-Arg-Arg-NH₂ have the broadest spectrum of antimicrobial activity and the lowest hemolytic activity. They are active against all 11 tested strains of Gram-positive bacteria, Gram-negative bacteria and fungi with MIC₅₀ from 0.9 to 6.1 μg/ml (0.5 to 3.2 μM), being up to 3 times more active than indolicidin, and are at least 1.8 times less hemolytically active than indolicidin (reached the detection limit). These peptides are patented and could be used for further drug development as antimicrobials.

Keywords: AMP; Antimicrobial peptide; biocide; drug design; indolicidin; screening.