Easy Strategy To Increase Salt Resistance of Antimicrobial Peptides

The efficacies of many antimicrobial peptides are greatly reduced under high salt concentrations, limiting their development as pharmaceutical compounds. Here, we describe an easy strategy to increase salt resistance of antimicrobial peptides by replacing tryptophan or histidine residues with the bulky amino acids -naph-thylalanine and -(4,4-biphenyl)alanine. The activities of the salt-sensitive peptide P-113 were diminished at high salt concentrations, whereas the activities of its -naphthylalanine and -(4,4-biphenyl)alanine-substi-tuted variant were less affected. Antimicrobial peptides play important roles in the host in-nate defense mechanism by interacting and permeabilizing mi-crobial membranes (21). With an increase of antibiotic resis-tance, the potential for the development of antimicrobial peptides as novel therapeutic agents could overcome the prob-lem of resistance (5). The development of antimicrobial peptides has been hin-dered by several problems. One of these problems is salt sensitivity (13). The efficacy of human -defensin-1 is greatl