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

Abstract 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. © 2005 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 5: 276–285; 2005: Published online in Wiley InterScience ( www.interscience.wiley.com ) DOI 10.1002/tcr.20051