Synthesis and biochemical evaluation of selective inhibitors of class II fructose bisphosphate aldolases: towards new synthetic antibiotics

Chemistry. 2008;14(28):8521-9. doi: 10.1002/chem.200800857.

Abstract

We report the synthesis and biochemical evaluation of selective inhibitors of class II (zinc-dependent) fructose bisphosphate aldolases. The most active compound is a simplified analogue of fructose bisphosphate, bearing a well-positioned metal chelating group. It is a powerful and highly selective competitive inhibitor of isolated class II aldolases. We report crystallographic studies of this inhibitor bound in the active site of the Helicobacter pylori enzyme. The compound also shows activity against Mycobacterium tuberculosis isolates.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology*
  • Crystallography
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Fructose-Bisphosphate Aldolase / antagonists & inhibitors*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Mycobacterium tuberculosis / drug effects

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Fructose-Bisphosphate Aldolase