Printed in Great Britain Des-, syn- and anti-oxyimino-A-cephalosporins Intrinsic reactivity and reaction with RTEM-2 serine A-lactamase and D-alanyl-D-alanine-cleaving serine

The presence and configuration (syn or anti) of an oxyimino group in the 7(f,)-acyl side chain of 3-cephems do not modify the intrinsic reactivity of the /3-lactam ring, but have highly enzyme-specific effects. When compared with the corresponding des-oxyimino P-lactam compound: (i) with the plasmid-mediated Escherichia coli RTEM-2 serine P-lactamase, the substrate activity of the anti isomer is increased and that of the syn isomer is decreased; (ii) with the Streptomyces R61 serine D-alanyl-D-alanine cleaving peptidase (a highly penicillin-sensitive enzyme), the rate ofenzyme acylation is not or only little affected when the oxyimino group is in the syn configuration, but is decreased when the oxyimino group is in the anti configuration; (iii) with the Actino-madura R39 serine D-alanyl-D-alanine-cleaving peptidase (an exceedingly highly penicillin-sensitive enzyme), the rate of enzyme acylation is unaffected whatever the configuration of the substituent. The oxidation of the sulphur atom of the dihydrothi-azine ring on the f-face of the molecule makes it both a poorer inactivator of the DD-peptidases and a poorer substrate of the f,-lactamase. The Streptomyces albus G Zn2 +-containing D-alanyl-D-alanine-cleaving peptidase (a highly penicillin-resistan