Amphiphilic Derivatives of L-Lysil-L-methionine, Differing in the Length of the Aliphatic Fragment in the Hydrophobic Block of Lipodipeptides

Abstract

The growth of antimicrobial resistance to traditional antibiotics over the past decades requires accelerating the pace of development of new approaches to reducing the activity of various infectious processes. Natural and synthetic antimicrobial peptides, as well as lipophilic low-molecular peptidomimetics, are considered as promising antibacterial agents. A scheme for obtaining and synthesizing a series of new amphiphiles based on amino acid derivatives with L-lysine residues in the polar block, L-methionine in the central fragment, and with variations in the length of the hydrocarbon radicals C₈–C₁₂ in the lipodipeptides is developed. The antibacterial activity of the synthesized samples is studied. They are highly effective against both Gram-positive and Gram-negative bacteria. Within the series, a parabolic dependence of the effectiveness of the antibacterial action on the length of the hydrocarbon radical is observed. The lead compound Lys-Met-C₁₁ with a MIC of 0.39 μg/mL has low cytotoxicity.