Reversible inhibitors of penicillinases.
Reversible competitive inhibitors of a penicillinase, beta-lactamase 1 from Bacillus cereus, were studied. These represent the first inhibitors of a penicillinase that lack the beta-lactam ring. The products of the enzymic reaction, namely penicilloic acids, are inhibitors; their decarboxylation products, the penilloic acids, are also inhibitors, and have somewhat lower Ki values. Inhibitors have been prepared from benzylpenicillin, phenoxymethyl-penicillin, methicillin (2,6-dimethoxybenzamidopenicillanic acid) and 3-hydroxy-4-nitrobenzamidopenicillanic acid. Decarboxylation of the penicilloic acids from benzyl-penicillin, or from phenoxymethylpenicillin, leads to epimerization (at C-5) of the penilloic acid. Nuclear-magnetic resonance spectroscopy at a frequency of 270 MHz can distinguish the epimers. Other competitive inhibitors studied were boric acid, benzene boronic acid and m-aminobenzeneboronic acid. Boric acid itself was the best inhibitor of beta-lactamase I so far found.
D001409:Bacillus cereus / Q000201:enzymology; D001888:Boric Acids / Q000494:pharmacology; D001897:Boronic Acids / Q000494:pharmacology; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010406:Penicillins / Q000138:chemical synthesis / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D065093:beta-Lactamase Inhibitors
D001888:Boric Acids; D001897:Boronic Acids; D010406:Penicillins; D065093:beta-Lactamase Inhibitors