The objectives of this proposal are to gain an understanding of the mechanism of amide hydrolysis by dinuclear metallohydrolases and the relationship between the coordination environment and the activity of the metal center. This will be done by modeling the active sites of dinuclear metallohydrolase enzymes using synthetic model complexes. A tunable, dinucleating phthalazine-based ligand system has been designed for use in this study. Dinuclear complexes of these ligands will be used to probe aspects of the proposed mechanism, and the ligand environment will be tuned to optimize hydrolytic activity. This study of hydrolytically viable dinuclear metal complexes will aid in the elucidation of hydrolytic metalloenzyme mechanisms, clarify the roles of the metal ions in these systems, and ultimately aid in the development of artificial hydrolases.
| Shenbagamurthi, P; Kundu, B; Raths, S et al. (1985) Biological activity and conformational isomerism in position 9 analogues of the des-1-tryptophan,3-beta-cyclohexylalanine-alpha-factor from Saccharomyces cerevisiae. Biochemistry 24:7070-6 |
