olivanic-acid and brobactam

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Chemical Phenomena; Chemistry; Clavulanic Acid; Clavulanic Acids; Gram-Negative Bacteria; Humans; Lactams; Penicillanic Acid; Sulfones

The mechanistic pathway followed by the E. coli RTEM beta-lactamase has been studied with a view to clarifying the mode of action of a number of recently discovered inactivators of the enzyme. There is clear evidence that the beta-lactamase-catalysed hydrolysis of the 7-alpha-methoxycephem, cefoxitin, proceeds via an acyl-enzyme intermediate. An analysis of the inactivation reactions of all the known beta-lactam derivatives that result in irreversible loss of enzyme activity permits the identification of three structural features required for a beta-lactamase inactivator. The application of these principles suggests a new group of mechanism-based inactivators of the enzyme: the sulphones of N-acyl derivatives of 6-beta-aminopenicillanic acid that are themselves poor substrates for the enzyme. These sulphones are powerful inactivators of the beta-lactamase.

Topics: Anti-Bacterial Agents; Bacteria; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Clavulanic Acid; Lactams; Penicillanic Acid; Sulbactam