Design of Reaction Catalysts Based on Protein Cavities

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With this Renewal award, the Organic and Macromolecular Chemistry Program is continuing support for Dr. Mark Distefano at the University of Minnesota - Twin Cities. The objectives of the work are to: 1) improve the activities and enantioselectivities of transaminating catalysts based on protein cavities of mutant FABPs (Fatty Acid Binding Proteins), 2) assess the effects of cofactor structure, 3) expand the scope of reaction types to include C-C bond formation, 4) develop methods to prepare and screen rapidly catalyst candidates, and 5) develop a phage display system to select protein cavities that can bind pyridoxamine analogues noncovalently. Dr. Distefano is developing a series of novel semisynthetic enzyme-like catalysts based on a class of proteins (FABPs) that contain a large empty central cavity, which can be used to hold organic substrates while they are operated on by cofactors that are chemically linked to the protein. The FABPs can be easily cloned and efficiently expressed, allowing considerable variability in their size and composition. Such catalysts could be very useful in the preparation of a wide variety of specialty chemicals. Because they operate in water under mild conditions and are prepared from biodegradable materials, they are also environmentally attractive.