Inhibiting dihydrodipicolinate synthase across species: towards specificity for pathogens?

Bioorg Med Chem Lett. 2008 Jan 15;18(2):842-4. doi: 10.1016/j.bmcl.2007.11.026. Epub 2007 Nov 13.

Abstract

Dihydrodipicolinate synthase (DHDPS) is a key enzyme in lysine biosynthesis and an important antibiotic target. The specificity of a range of heterocyclic product analogues against DHDPS from three pathogenic species, Bacillus anthracis, Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus, and the evolutionarily related N-acetylneuraminate lyase, has been determined. The results suggest that the development of species-specific inhibitors of DHDPS as potential antibacterials is achievable.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus anthracis / enzymology
  • Enzyme Inhibitors / pharmacology
  • Hydro-Lyases / antagonists & inhibitors*
  • Mycobacterium tuberculosis / enzymology
  • Species Specificity
  • Staphylococcus aureus / enzymology

Substances

  • Enzyme Inhibitors
  • Hydro-Lyases
  • 4-hydroxy-tetrahydrodipicolinate synthase