New analogs of temporin-LK1 as inhibitors of multidrug-resistant (MDR) bacterial pathogens

Abstract

<p>The peptide temporin-LK1 (<b>1</b>) was obtained from the skin secretion of frog <i>Limnonectes kuhlii</i> (Ranidae). It is a unique antimicrobial peptide with 17 residues, including four L-phenylalanines and single glycine. Mass spectrometry and Edmand degradation were used for the determination of sequence of amino acids in temporin-LK 1 (<b>1</b>), and confirmed by cDNA cloning. We report here the synthesis and structural studies of temporin-LK1 (<b>1</b>) and its analogs <b>2–4</b>. Peptides <b>2</b>–<b>4</b> were prepared by substitution of achiral glycine residue of temporin-LK1 (<b>1</b>) with D-alanine, L-phenylglycine, and L-naphthylalanine, respectively. Peptides <b>1–4</b> were evaluated against multidrug-resistant (MDR) strains of <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>. Analog <b>2</b> was found active against all MDR strains of <i>S. aureus</i> and <i>P. aeruginosa</i> at a much lower dose than the clinically used antibiotics.</p