Molecular Pharmacology, Vol 14, 704-709, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

Conformation Patterns in Penicillins and the Penicillin-Penicillinase Interaction

¹ Departments of Molecular Biology and Organic Chemistry, Hebrew University, Jerusalem, Israel

Conformational energy maps have been computed for three penicillin derivatives by the quantum mechanical method of perturbative configuration interaction using localized orbitals (PCILO). It was found that rotation about the C—N bond to the acyl side chain is quite hindered, with a preferred conformation that is practically independent of the side chain. However, the energetics of rotation about axes in the side chain depend greatly on its structure. The computed patterns permit two types of penicillin derivatives to be distinguished. This differentiation is parallel to the experimental classification of penicillins as S- or A-type by the mode of their interaction with penicillinase. An interpretation of this parallelism is proposed.