Effect of 7-α methoxy substitution of cephalosporins upon their affinity for the penicillin-binding proteins of E. coti K12 Comparison with antibacterial activity and inhibition of membrane bound model transpeptidase activity

Abstract

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.