Poly(2-Oxazoline)-Based Functional Peptide Mimics: Eradicating MRSA Infections and Persisters while Alleviating Antimicrobial Resistance

Angew Chem Int Ed Engl. 2020 Apr 16;59(16):6412-6419. doi: 10.1002/anie.202000505.

Abstract

Peptides have important biological functions. However, their susceptibility to proteolysis limits their applications. We demonstrated here for the first time, that poly(2-oxazoline) (POX) can work as a functional mimic of peptides. POX-based glycine pseudopeptides, a host defense peptide mimic, had potent activities against methicillin-resistant S. aureus, which causes formidable infections. The POX mimic showed potent activity against persisters that are highly resistant to antibiotics. S. aureus did not develop resistance to POX owning to the reactive oxygen species related antimicrobial mechanism. POX-treated S. aureus is sensitive to common antibiotics, demonstrating no observable antimicrobial pressure or cross-resistance in using antimicrobial POX. This study highlights POX as a new type of functional mimic of peptides and opens new avenues in designing and exploring peptide mimetics for biological functions and applications.

Keywords: antibiotics; antimicrobials; drug design; peptides; polymers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / chemical synthesis
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology*
  • Drug Resistance, Bacterial / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Microbial Sensitivity Tests
  • Oxazoles / chemistry*
  • Peptidomimetics / chemical synthesis
  • Peptidomimetics / chemistry*
  • Peptidomimetics / pharmacology
  • Reactive Oxygen Species / metabolism
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / metabolism

Substances

  • Anti-Infective Agents
  • Oxazoles
  • Peptidomimetics
  • Reactive Oxygen Species
  • poly(2-oxazoline)