The focus of this research is the investigation of new approaches for the design and production of catalytic antibodies. In general, antibodies raised to compounds that resemble transition states of a desired reaction are expected to use binding forces to lower the energy of a real transition state in the analogous chemical transformation. Catalytic rate enhancements as high as one million-fold over background have been observed using this strategy. Exquisite substrate specificity, including stereospecificity when appropriate, is always observed, and this specificity can be programmed into the antibody by the structure of the original immunizing haptens. There are three major projects, all designed to exploit this programmable specificity of catalytic antibodies. In each case, standard hybridoma techniques for production of monoclonal antibodies in mice enhanced by new molecular biology methods will be used. The first project will probe the use of catalytic antibodies to manipulate chemical protecting groups during organic synthesis. The second project involves testing the utility of metal cofactors in antibody catalyzed reactions. The third project seeks to generate an antibody-based system that can reproduce some of the essential features of photosynthesis. %%% With this Presidential Young Investigator Award, the Synthetic Organic Program of the Chemistry Division will support the research of Dr. Brent Iverson of the Department of Chemistry and Biochemistry at the University of Texas at Austin on catalytic antibodies. These antibodies, produced by challenging the immune systems of mice with compounds that resemble high energy or transition states of desired reactions, frequently are capable of providing catalytic rate enhancements as high as one million-fold. Thus these antibodies resemble enzymes in being catalytic proteins, but function to catalyze reactions for which no enzymes exist.
