Converting Teixobactin into a Cationic Antimicrobial Peptide (AMP)

J Med Chem. 2017 Sep 14;60(17):7476-7482. doi: 10.1021/acs.jmedchem.7b00834. Epub 2017 Aug 23.

Abstract

Teixobactin is a head to side chain cyclodepsipeptide that contains two positive charges. One is found in the cycle, as a result of the presence of the guanidino-unusual amino acid L-allo-End, while the other is at the N-terminal. Here we introduce 26 new Teixobactin analogues with an increasing number of positive charges. In an attempt to fine-tune the biological activity of Teixobactin, we examined the effect of cationicity on the SAR of these analogues. The maximum number of positive charges to maintain the activity are three to four. Analogues with five positive charges show the lowest activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / chemistry*
  • Antimicrobial Cationic Peptides / pharmacology*
  • Bacteria / drug effects
  • Bacterial Infections / drug therapy
  • Depsipeptides / chemistry*
  • Depsipeptides / pharmacology*
  • Humans
  • Microbial Sensitivity Tests

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Depsipeptides
  • teixobactin