Combinatorial approach toward synthesis of small molecule libraries as bacterial transglycosylase inhibitors

Org Biomol Chem. 2010 Jun 7;8(11):2586-93. doi: 10.1039/c000622j. Epub 2010 Mar 29.

Abstract

The development of iminocyclitol-based small molecule libraries against a bacterial TGase is described. An iminocyclitol was conjugated with a pyrophosphate mimic using either a 1,3-dipolar cycloaddition or reductive amination reaction, which was then condensed with a variety of lipophilic carboxylic acids in an amide bond coupling to generate a desired molecular library. With assistance of microtiter plate-based combinatorial chemistry and in situ screening, a potential inhibitor, the first potent iminocyclitol-based inhibitor against bacterial TGases was efficiently developed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry*
  • Bacteria / enzymology*
  • Combinatorial Chemistry Techniques*
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry*
  • Glycosyltransferases / antagonists & inhibitors*
  • Molecular Structure
  • Small Molecule Libraries / chemical synthesis*
  • Small Molecule Libraries / chemistry

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Small Molecule Libraries
  • Glycosyltransferases