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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 ␤-naphthylalanine 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-substituted variant were less affected.

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