The long-term goal of this research program is to develop highly- selective synthetic catalysts that, like enzymes, have the ability to recognize and selectively modify their substrates. Catalysts of this sort will facilitate the efficient commercial production of important therapeutics. In pursuing this goal, we hope to make contributions to design principles in supramolecular catalysis. We will use combinatorial chemistry to prepare catalyst libraries, thermographic kinetic analysis to select effective catalysts from these libraries and thermodynamic binding assays to study general relationships between substrate binding and catalysis. In accord with this goal, the specific aims of the proposal are: 1) to develop and define a general method that, based on kinetic analysis, allows selection of effective catalysts from large collections of polymer-bound compounds prepared through split-pool combinatorial synthesis, 2) to use kinetic and thermodynamic library analysis to develop and characterize catalysts that have the ability to modify peptides with sequence selectivity, 3) to develop and characterize multi-functional catalysts that recognize transition states and facilitate enantioselective chemical reaction.
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