Conformationally constrained diketopimelic acid analogues as inhibitors of dihydrodipicolinate synthase

Berin A Boughton; Renwick C J Dobson; Juliet A Gerrard; Craig A Hutton

doi:10.1016/j.bmcl.2007.11.108

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.

Authors

Berin A Boughton¹, Renwick C J Dobson, Juliet A Gerrard, Craig A Hutton

Affiliation

¹ School of Chemistry, University of Melbourne, Vic. 3010, Australia.

PMID: 18077163
DOI: 10.1016/j.bmcl.2007.11.108

Abstract

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*

Substances

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