EFFECT OF 7-ALPHA METHOXY SUBSTITUTION OF CEPHALOSPORINS UPON THEIR AFFINITY FOR THE PENICILLIN-BINDING PROTEINS OF ESCHERICHIA-COLI-K12 - COMPARISON WITH ANTIBACTERIAL ACTIVITY AND INHIBITION OF MEMBRANE-BOUND MODEL TRANSPEPTIDASE ACTIVITY

7-α methoxy substitution of cefuroxime, cephamandole, cephapirin and cephalosporin 87/359 was found to have a marked effect upon affinity of the β-lactam antibiotics for the penicillin-binding proteins of Escherichia coli K12.The 7-α methoxy (cephainycin) derivatives had no affinity for PBP2, a reduced affinity for PBP3 and, with the exception of cefoxitin, (7-α methoxy 87/359), a reduced affinity for PBPs la/lb, compared to their non-7-α methoxy counterparts.Also, the 7-α methoxy substitution greatly enhanced the binding of the antibiotics to PBPs 5/6, which correlated with their increased inhibitory activity for membrane bound model transpeptidase activity in E. coli K12.These results are discussed in relation to the antibacterial activity of the compounds against a wild-type strain and an isogenic permeability mutant of E. coli K12. © 1979, by The British Society for Antimicrobial Chemotherapy.