Conformationally constrained diketopimelic acid analogues as inhibitors of dihydrodipicolinate synthase.
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.
Boughton
Berin A
BA
School of Chemistry, University of Melbourne, Vic. 3010, Australia.
Dobson
Renwick C J
RC
Gerrard
Juliet A
JA
Hutton
Craig A
CA
D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D010867:Pimelic Acids / Q000737:chemistry* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D010867:Pimelic Acids; D006836:Hydro-Lyases; C020040:4-hydroxy-tetrahydrodipicolinate synthase