Synthesis and biological evaluation of potential new inhibitors of the bacterial transferase MraY with a β-ketophosphonate structure

Org Biomol Chem. 2011 Dec 21;9(24):8301-12. doi: 10.1039/c1ob06124k. Epub 2011 Nov 1.

Abstract

Stable analogs of bacterial transferase MraY substrate or product with a pyrophosphate surrogate in their structure are described. β-ketophosphonates were designed as pyrophosphate bioisosteres and were investigated as UDP-GlcNAc mimics. The developed strategy allows introduction of structural diversity at a late stage of the synthesis. The biological activity of the synthesized compounds was evaluated on the MraY enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus subtilis / enzymology*
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Biocatalysis
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Molecular Conformation
  • Organophosphonates / chemical synthesis
  • Organophosphonates / chemistry
  • Organophosphonates / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Transferases (Other Substituted Phosphate Groups)
  • Transferases / antagonists & inhibitors*
  • Transferases / metabolism

Substances

  • Bacterial Proteins
  • Enzyme Inhibitors
  • Organophosphonates
  • Transferases
  • Transferases (Other Substituted Phosphate Groups)
  • mraY protein, Bacteria