Antimicrobial peptides containing unnatural amino acid exhibit potent bactericidal activity against ESKAPE pathogens

Rickey Paige Hicks, J. J. Abercrombie, R. K. Wong, K. P. Leung

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

A series of 36 synthetic antimicrobial peptides containing unnatural amino acids were screened to determine their effectiveness to treat Enterococcus faecium, Staphylococcus aureus, Klebsiella pnemoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) pathogens, which are known to commonly infect chronic wounds. The primary amino acid sequences of these peptides incorporate either three or six dipeptide units consisting of the unnatural amino acids Tetrahydroisoquinolinecarboxylic acid (Tic) and Octahydroindolecarboxylic acid (Oic). The Tic-Oic dipeptide units are separated by SPACER amino acids with specific physicochemical properties that control how these peptides interact with bacterial cell membranes of different chemical compositions. These peptides exhibited minimum inhibitory concentrations (MIC) against these pathogens in the range from >100 to 6.25 μg/mL. The observed diversity of MIC values for these peptides against the various bacterial strains are consistent with our hypothesis that the complementarity of the physicochemical properties of the peptide and the lipid of the bacteria's cell membrane determines the resulting antibacterial activity of the peptide.

Original languageEnglish (US)
Pages (from-to)205-214
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2013

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Keywords

  • Antimicrobial peptides
  • Cellular toxicity
  • ESKAPE
  • MBC
  • MIC
  • Unusual amino acids

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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