Structure-activity relationships of penem antibiotics: Crystallographic structures and implications for their antimicrobial activities

Twelve closely related crystal structures of the penem derivatives revealed a characteristic short contact of the oxygen atom in the C2 side-chains with the S1 atom. The side-chain conformations of the crystal structures showed a good correlation with the antimicrobial activity. In particular, the penems which show high antimicrobial activity have similar torsion angles for S1-C2-C1′-C2′, suggesting that the disposition of the C2′ atom would be important for binding to penicillin-interacting enzymes. Two conformations of the C6 hydroxyethyl group were observed in the crystal structures. Of those two, the conformation with a larger torsion angle ( δ = 179.2°) is deduced to be the enzyme-bound conformation in the Michaelis complex. Twelve closely related crystal structures of the penem derivatives revealed a characteristic short SO contact. The side-chain conformations of the crystal structures showed a good correlation with the antimicrobial activity.