Paul A O'Donnell

Publications (2)5.64 Total impact

• Article: LC-MS and NMR characterization of the purple chromophore formed in the o-aminobenzaldehyde assay of dihydrodipicolinate synthase.

  Voula Mitsakos, Sean R A Devenish, Paul A O'Donnell, Juliet A Gerrard, Craig A Hutton
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  ABSTRACT: The enzyme dihydrodipicolinate synthase (DHDPS) has been widely investigated as a target for new antibiotics. The o-aminobenzaldehyde (o-ABA) assay is routinely used as a highly specific, if qualitative, tool for DHDPS purification, whereby fractions containing active DHDPS appear purple upon addition of o-ABA. The purple adduct absorbs in the visible region (540 nm) but has never been characterized in the 50 years since it was first reported. Structural characterization of this purple compound has been performed by UV spectrophotometry, NMR spectroscopy and tandem mass spectrometry. The extinction coefficient of this chromophore was also determined.
  Bioorganic & medicinal chemistry 02/2011; 19(4):1535-40. · 2.82 Impact Factor
• Article: Irreversible inhibition of dihydrodipicolinate synthase by 4-oxo-heptenedioic acid analogues.

  Berin A Boughton, Michael D W Griffin, Paul A O'Donnell, Renwick C J Dobson, Matthew A Perugini, Juliet A Gerrard, Craig A Hutton
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  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.
  Bioorganic & medicinal chemistry 01/2009; 16(23):9975-83. · 2.82 Impact Factor