Journal article

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

Berin A Boughton, Michael DW Griffin, Paul A O'Donnell, Renwick CJ Dobson, Matthew A Perugini, Juliet A Gerrard, Craig A Hutton

BIOORGANIC & MEDICINAL CHEMISTRY | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2008

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.