Mechanism-based library

Combinatorial chemists at Merck described the synthesis of a mechanism-based library (1.25) of matrix metallo-protease inhibitors combining both mix and split and indexed combinatorial techniques [10]. The results found in the study were consistent with the known SAR for this class of inhibitor. 

Targeted libraries have been most effective when based upon the display of diverse functionality about a minimal mechanism-based pharmacophore targeting an enzyme family. Early successes with this approach were first achieved with proteases.1221 Our own efforts to design libraries which target enzyme families require that the minimal pharmacophore serves as the site for attachment to solid support.1231 The pharmacophore is the only invariant part of the inhibitor structure, which... 

C. E. Lee, E. K. Kick, J. A. Ellman, General Solid-Phase Synthesis Approach to Prepare Mechanism-Based Aspartyl Protease Inhibitor Libraries. Identification of Potent Cathepsin D Inhibitors. J. Am. Chem. Soc 1998, 120, 9735-9747. 

The similarities concerning the bound cofactors, the reaction mechanism, and the adenine-binding pockets led to a screen of the above-described purine-based library of ATP-competitive inhibitors originally designed to target CDKs for crossreactivity with the carbohydrate sulfotransferase NodH from Rhizobium meliloti. 

Wood WJL, Huang L, Elknan JA. Synthesis of a diverse library of mechanism-based cysteine protease inhibitors. J. Comb. Chem. 2003 5 869-880. 

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