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Broadening the Aldolase Catalytic Antibody Repertoire by Combining Reactive Immunization and Transition State Theory:

Zhong1, Lerner, Barbas

  • 1The Skaggs Institute for Chemical Biology and, The Department of Molecular Biology, The Scripps Research Institute, 10 550, North Torrey Pines Road, La Jolla, CA 92037 (USA).

Nine efficient aldolase antibodies were generated by using hapten 1. This hapten unites reactive immunization and the transition state analogue approach in a single molecule. Characterization of two of these antibodies reveals that they are highly proficient (up to 1000-fold better than any other antibody catalyst) and enantioselective catalysts for aldol and retro-aldol reactions and exhibit enantio- and diastereoselectivities opposite to that of antibody 38C2.

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