New developments in cytochrome P - 450 modeling

Presented here are the results of recent studies wfii-&-Gre designed to: ( 1 ) evaluate the role of the thiolate ligand, which is characteristic of P-450 structure, by incorporating it into model systems; ( 2 ) synthesize polypeptide-bound porphyrin to investigate the effects of heme environment on the activities; ( 3 ) apply appropriately designed P-450 mimics to drug metabolism studies and evaluate their utility. Cytochrome P-450 plays an important role in metabolizing biomolecules and xenobiotics, and the mechanism of its catalytic activities and structural functions have been the subject of extensive investigation in the field o f biomimetic chemistry(ref. 1 ) . We have achieved the synthesis of many effective P-450 mimics and clarified their functions with the aim of developing artificial enzymes having high similarity to the native P-450 system for investigating drug metabolism. Here we present three recent topics in our studies; the evaluation of the effect of the axial ligand and apoprotein by incorporation into model systems, and the application o f appropriately designed P-450 mimics to drug metabolism studies .