Intramolecular cooperativity in the reaction of diacyl phosphates with serine beta-lactamases.

ABSTRACT: Asymmetric diaroyl phosphates (ArCOOPO(2)(-)OCOAr', where Ar = Ph, Ar' = 4-biphenyl, 2-benzothiophenyl and 2-benzofuranyl) have been prepared, evaluated as serine (classes A, C, and D) beta-lactamase inhibitors, and compared with respect to the latter with their symmetric parents, where Ar = Ar'. The asymmetric compounds, in general, were found to react with the beta-lactamases in two modes, corresponding to different orientations with respect to the active site, whereby either of the two aroyl groups may acylate the enzyme to form two different inert acyl-enzymes, E-COAr and E-COAr' . In all cases, the asymmetric compounds, in one orientation, react more rapidly with the enzymes tested than one symmetrical parent but not both. From comparisons of activation free energy differences, it was

SUBMITTER: Majumdar S 

PROVIDER: S-EPMC2885897 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature