Heterocyclic inhibitors of dihydrodipicolinate synthase are not competitive.
A series of piperidine- and pyridine-2,6-dicarboxylate derivatives has been evaluated as potential inhibitors of dihydrodipicolinate synthase (DHDPS). The compounds were designed with oxygen functionality at the C-4 position in order to mimic the putative enzyme product HTHDP. Most compounds displayed weak-moderate inhibition of DHDPS. Additionally, the most potent inhibitors were shown not to be competitive, indicating they do not bind at the active site. Discrepancies between the two common assay systems-the imidazole assay and the coupled assay-were observed which are attributed to inherent problems in the imidazole assay, leading to artefactually low K(i) measurements.
Turner
Jennifer J
JJ
School of Chemistry, University of Sydney, Sydney, NSW 2006, Australia.
Gerrard
Juliet A
JA
Hutton
Craig A
CA
D001667:Binding, Competitive; D003500:Cyclization; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007700:Kinetics; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry; D013455:Sulfur / Q000737:chemistry
D004791:Enzyme Inhibitors; D013455:Sulfur; D006836:Hydro-Lyases; C020040:4-hydroxy-tetrahydrodipicolinate synthase; D009584:Nitrogen