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

…, PA O'Donnell, RCJ Dobson, MA Perugini…

Index: Boughton, Berin A.; Griffin, Michael D.W.; O'Donnell, Paul A.; Dobson, Renwick C.J.; Perugini, Matthew A.; Gerrard, Juliet A.; Hutton, Craig A. Bioorganic and Medicinal Chemistry, 2008 , vol. 16, # 23 p. 9975 - 9983

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Citation Number: 22

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 ...