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ID: ALA1151703

Journal: Bioorg Med Chem

Title: Irreversible inhibition of dihydrodipicolinate synthase by 4-oxo-heptenedioic acid analogues.

Authors: Boughton BA, Griffin MD, O'Donnell PA, Dobson RC, Perugini MA, Gerrard JA, Hutton CA.

Abstract: We report the synthesis of (2E,5E)-4-oxoheptadienedioic acid and (2E)-4-oxoheptenedioic acid and evaluation of both diester and diacid analogues as inhibitors of bacterial dihydrodipicolinate synthase. Enzyme kinetic studies allowed the determination of second-order rate constants of inactivation; and substrate co-incubation studies have shown the inhibitors act at the active-site. Mass spectrometric analyses have further explored the enzyme-inhibitor interaction and determined the sites of enzyme alkylation.

CiteXplore: 18977662

DOI: 10.1016/j.bmc.2008.10.026