Reference : Kinetic Study of Two Novel Enantiomeric Tricyclic Beta-Lactams Which Efficiently Inac...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/28928
Kinetic Study of Two Novel Enantiomeric Tricyclic Beta-Lactams Which Efficiently Inactivate Class C Beta-Lactamases
English
Vilar, M. [> > > >]
Galleni, Moreno mailto [Université de Liège - ULg > Département des sciences de la vie > Macromolécules biologiques, Centre d'Ingénierie des Protéines > >]
Solmajer, T. [> > > >]
Turk, B. [> > > >]
Frère, Jean-Marie mailto [Université de Liège - ULg > Département des sciences de la vie > Enzymologie, Centre d'Ingénierie des Protéines > >]
Matagne, André mailto [Université de Liège - ULg > Département des sciences de la vie > Enzymologie, Centre d'Ingénierie des Protéines > >]
Aug-2001
Antimicrobial Agents and Chemotherapy
45
8
2215-23
Yes (verified by ORBi)
International
0066-4804
[en] A detailed kinetic study of the interaction between two ethylidene derivatives of tricyclic carbapenems, Lek 156 and Lek 157, and representative beta-lactamases and D-alanyl-D-alanine peptidases (DD-peptidases) is presented. Both compounds are very efficient inactivators of the Enterobacter cloacae 908R beta-lactamase, which is usually resistant to inhibition. Preliminary experiments indicate that various extended-spectrum class C beta-lactamases (ACT-1, CMY-1, and MIR-1) are also inactivated. With the E. cloacae 908R enzyme, complete inactivation occurs with a second-order rate constant, k(2)/K', of 2 x 10(4) to 4 x 10(4) M(-1) s(-1), and reactivation is very slow, with a half-life of >1 h. Accordingly, Lek 157 significantly decreases the MIC of ampicillin for E. cloacae P99, a constitutive class C beta-lactamase overproducer. With the other serine beta-lactamases tested, the covalent adducts exhibit a wide range of stabilities, with half-lives ranging from long (>4 h with the TEM-1 class A enzyme), to medium (10 to 20 min with the OXA-10 class D enzyme), to short (0.2 to 0.4 s with the NmcA class A beta-lactamase). By contrast, both carbapenems behave as good substrates of the Bacillus cereus metallo-beta-lactamase (class B). The Streptomyces sp. strain R61 and K15 extracellular DD-peptidases exhibit low levels of sensitivity to both compounds.
http://hdl.handle.net/2268/28928

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