Effect of the lipid II sugar moiety on bacterial transglycosylase: the 4-hydroxy epimer of lipid II is a TGase inhibitor

Chem Commun (Camb). 2017 Jan 5;53(4):771-774. doi: 10.1039/c6cc07871k.

Abstract

Lipid II analogues bearing major modifications on the second sugar (GlcNAc) were synthesized and evaluated for their substrate activity toward TGases. Unexpectedly, N-deacetyled lipid II decreased its activity dramatically, and the C4-axial OH lipid II became an inhibitor (IC50 = 8 μM) with an approximately 14-fold increase in binding affinity toward TGase (25 vs. 27).

MeSH terms

  • Clostridioides difficile / enzymology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Escherichia coli / enzymology*
  • Lipids / chemistry
  • Lipids / pharmacology*
  • Peptidoglycan Glycosyltransferase / antagonists & inhibitors*
  • Peptidoglycan Glycosyltransferase / metabolism
  • Structure-Activity Relationship
  • Substrate Specificity
  • Sugars / chemical synthesis
  • Sugars / chemistry
  • Sugars / pharmacology*

Substances

  • Enzyme Inhibitors
  • Lipids
  • Sugars
  • Peptidoglycan Glycosyltransferase