Matrix metalloprotease inhibitors design

R 303 B. Bluemich, S. Anferova, F. Casanova, K. Kremer, J. Perlo and S. Sharma, Unilateral NMR Principles and Applications to Quality Control of Elastomer Products , KGK, Kaut.Gummi Kunstst., 2004,57,346 R 304 PJ. Bond and M.S. Sansom, The Simulation Approach to Bacterial Outer Membrane Proteins (Review) , Mol.Membr.Biol., 2004,21,151 R 305 N. Borkakoti, Matrix Metalloprotease Inhibitors Design from Structure , Biochem.Soc.Trans., 2004,32,17... 

M. Whittaker, C. D. Floyd, P. Brown and A. J. H. Gearing, Design and therapeutic application of matrix metalloprotease inhibitors, Chem. Rev. 1999, 99, 2735-2776. 

J. W. Skiles, N. C. Gonnella, A. Y. Jeng, The Design, Structure, and Therapeutic Application of Matrix Metalloprotease Inhibitors, Curr. Med. Chem. 2001, 8, 425-474. 

Matter, H. and Schudok, M. (2004) Recent advances in the design of matrix metalloprotease inhibitors. Current Opinion in Drug Discovery S, Development, 7, 513-535. 

The metalloproteases (MPs) and matrix metalloproteinases (MMPs) are a class of metallohydrolases of particular interest to the pharmaceutical industry due to their role in a number of pathological processes [81-83], The lack of an enzyme-bound nucleophilic residue in the metallohydrolases complicates the design of ABPP probes for this class of enzymes. Rather than mechanism-based and electrophilic probes for ABPP, photoreactive variants of reversible inhibitors of metallohydrolases have been developed [84-86]. These reversible inhibitors usually contain a hydroxamate moiety that is capable of chelating the catalytic zinc ion in a bidentate manner [79, 80]. The hydroxamate moiety was incorporated into the first generation of metallohydrolase ABPP probes along with a benzophenone group capable of covalent bond formation upon UV irradiation (Scheme 4). 

---