Direct modifications of the cyclic peptide Polymyxin B leading to analogues with enhanced in vitro antibacterial activity

Bioorg Med Chem Lett. 2020 Jun 1;30(11):127163. doi: 10.1016/j.bmcl.2020.127163. Epub 2020 Mar 30.

Abstract

Synthetic modifications have been made directly to the cyclic peptide core of polymyxin B, enabling the further understanding of structure activity relationships of this antimicrobial peptide. Such modified polymyxins are also substrates for enzymic hydrolysis, enabling the synthesis of a variety of semi-synthetic analogues, resulting in compounds with increased in vitro antibacterial activity.

Keywords: Antibiotics; Drug resistance; Gram negative; Peptides; Polymyxins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Escherichia coli / drug effects
  • Humans
  • Hydrolysis
  • Microbial Sensitivity Tests
  • Peptides, Cyclic / chemistry
  • Polymyxin B / chemical synthesis
  • Polymyxin B / chemistry*
  • Polymyxin B / pharmacology
  • Pseudomonas aeruginosa / drug effects
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Peptides, Cyclic
  • Polymyxin B