An understanding of the molecular basis of action, or mechanism, of proteolytic enzymes is a long-term objective of biochemical investigation, realization of which would have multiple benefits with regard to medical problems associated with protein metabolism. For metalloproteases, it is proposed to develop a new class of transition state-analog inhibitors based upon the phenol and upon the sulfone imine functional groups, for which preliminary evidence has indicated unusual efficacy. These promise to provide unique insight into the peptide cleavage mechanism. Also to be investigated are proline-specific proteases, which represent a previously underdeveloped topic. New designs of affinity labels and mechanism-based inactivators have been devised. A specific feature of the latter effort is broad potential applicability of materials so developed to a range of current developments in protein chemistry.
| Mock, W L; Cheng, H (2000) Principles of hydroxamate inhibition of metalloproteases: carboxypeptidase A. Biochemistry 39:13945-52 |
| Mock, W L; Wang, L (1999) Synergistic inhibition of carboxypeptidase A by zinc ion and imidazole. Biochem Biophys Res Commun 257:239-43 |
| Mock, W L; Xu, D (1999) Catalytic activity of carboxypeptidase B and of carboxypeptidase Y with anisylazoformyl substrates. Bioorg Med Chem Lett 9:187-92 |
| Mock, W L; Yao, J (1997) Kinetic characterization of the serralysins: a divergent catalytic mechanism pertaining to astacin-type metalloproteases. Biochemistry 36:4949-58 |
| Mock, W L; Liu, Y; Stanford, D J (1996) Arazoformyl peptide surrogates as spectrophotometric kinetic assay substrates for carboxypeptidase A. Anal Biochem 239:218-22 |
| Mock, W L; Stanford, D J (1996) Arazoformyl dipeptide substrates for thermolysin. Confirmation of a reverse protonation catalytic mechanism. Biochemistry 35:7369-77 |
