Development of protein, peptide, and small molecule catalysts using catalysis-based selection strategies

We have developed peptide catalysts and antibody catalysts that catalyze aldol, retro-aldol, and Michael reactions via an enamine mechanism using reaction-based selections with 1,3-diketone derivatives. Nucleophilic amino groups of the catalysts were covalently trapped during the selections. We have also developed fluorogenic substrates that are useful for real-time monitoring of the progress of bond-forming reactions, such as aldol reactions, by an increase in fluorescence. These fluorogenic substrates have been used to monitor peptide-catalyzed, antibody-catalyzed, enzyme-catalyzed, and small molecule-catalyzed reactions. Catalysis-based screening using fluorogenic substrates will accelerate rapid identification of superior catalysts and reaction conditions.