Interaction of the novel penem CGP 31 608 and Its enantiomer with type Id beta-lactamase and penicillin-binding proteins

The novel penem CGP 31 608 (5R, 6S, 8R) and its enantiomer CGP 32 879 (5S, 6R, 8S) were shown to be essentially stable against hydrolysis by type Id-lactamase isolated fromPseudomonas aeruginosa18S/H. CGP 31 608 was a potent progressive inhibitor of this enzyme (I50=32M), which was only weakly inhibited by CGP 32 879 (I50=460M). CGP 31 608 had the highest affinity for penicillin-binding protein (PBP) 4 fromEscherichia coliK-12 (I50= 1g/ml), followed by PBPs 2 (10g/ml) and 1A/1Bs (100g/ml); CGP 32 879 did not inhibit binding of¹⁴C-benzylpenicillin to the PBPs. The steric configuration of the-lactam nucleus of penems appears to strongly influence their affinity for-Iactamases and target PBPs. The balanced spectrum of CGP 31 608 may be explained by its-lactamase stability and affinity for several vital PBPs.