Influence of methoxy-substitution of beta-lactam compounds on the interaction with various beta-lactamases.
The interaction of 6 alpha-(temocillin) and 7 alpha-methoxy substituted (cefoxitin) beta-lactam compounds with various beta-lactamases was studied employing enzyme kinetics and compared to that of unsubstituted compounds. Both chromosomally mediated enzymes from Enterobacter cloacae and Citrobacter freundii were competitively inhibited by the methoxy-substituted compounds. Higher concentrations of cefoxitin caused a competitive inhibition of the plasmid-mediated Tem-1 enzyme, whereas temocillin led to a non-competitive inhibition of the Tem-1 enzyme. These results indicate that the discrepancies in the interaction on the above mentioned compounds have to be attributed to the different molecular structure of the beta-lactam nucleus. Moreover, no predictions can be made on the basis of an analogy between 6 alpha-methoxy-penams and 7 alpha-methoxy cephems.
D001667:Binding, Competitive; D002440:Cefoxitin / Q000378:metabolism; D002510:Cephalosporinase / Q000378:metabolism*; D002511:Cephalosporins / Q000378:metabolism*; D002512:Cephalothin / Q000378:metabolism; D002876:Chromosomes, Bacterial; D002954:Citrobacter / Q000201:enzymology; D004754:Enterobacter / Q000201:enzymology; D004926:Escherichia coli / Q000201:enzymology; D007700:Kinetics; D010405:Penicillinase / Q000378:metabolism*; D010406:Penicillins / Q000378:metabolism*; D010957:Plasmids; D013982:Ticarcillin / Q000378:metabolism; D001618:beta-Lactamases / Q000378:metabolism*
D002511:Cephalosporins; D010406:Penicillins; C031367:temocillin; D002440:Cefoxitin; D002510:Cephalosporinase; D010405:Penicillinase; D001618:beta-Lactamases; D013982:Ticarcillin; D002512:Cephalothin