Amphiphilic cyclic peptoids that exhibit antimicrobial activity by disrupting Staphylococcus aureus membranes

Mia L. Huang, Meredith A. Benson, Sung Bin Y. Shin, Victor J. Torres, Kent Kirshenbaum

Research output: Contribution to journalArticle

Abstract

There is a significant unmet need for new antimicrobial agents that can address antimicrobial resistance. One promising group of antimicrobials is the antimicrobial peptides (AMPs) and their synthetic mimics. In particular, synthetic sequence-specific oligomers of N-substituted glycine, termed "peptoids", have been found to show potent antimicrobial activity against bacterial pathogens in vitro and can act against the emergence of antimicrobial resistance. In this study, we evaluate the antimicrobial activity of cyclic peptoid oligomers against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). The presence of the macrocyclic constraints can enforce a globally amphiphilic organization of the peptoid side-chains. Several of these new amphiphilic compounds show potent and selective antimicrobial activity. Electron microscopy experiments demonstrate that the peptoids target and damage the MRSA cytoplasmic membrane through the formation of pores. These results substantiate the potential of peptoids as antimicrobial therapeutic agents for the treatment of S. aureus infections.

Original languageEnglish (US)
Pages (from-to)3560-3566
Number of pages7
JournalEuropean Journal of Organic Chemistry
Issue number17
DOIs
StatePublished - Jun 2013

Keywords

  • Antibiotics
  • Foldamers
  • Macrocycles
  • Medicinal chemistry
  • Peptidomimetics

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

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