Conformationally constrained diketopimelic acid analogues as inhibitors of dihydrodipicolinate synthase

Bioorg Med Chem Lett. 2008 Jan 15;18(2):460-3. doi: 10.1016/j.bmcl.2007.11.108. Epub 2007 Dec 3.


Dihydrodipicolinate synthase (DHDPS) is a key enzyme in lysine biosynthesis and a potential antibiotic target. The enzyme catalyses the condensation of (S)-aspartate semi-aldehyde (ASA) and pyruvate to form dihydrodipicolinate. Constrained diketopimelic acid derivatives have been designed as mimics of the acyclic enzyme-bound condensation product of ASA and pyruvate. Several of the compounds are shown to be active, slow-binding inhibitors with improved inhibition of DHDPS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Hydro-Lyases / antagonists & inhibitors*
  • Molecular Conformation
  • Pimelic Acids / chemistry*
  • Pimelic Acids / pharmacology*


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