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Science 15 December 1995:
Vol. 270. no. 5243, pp. 1797 - 1800
DOI: 10.1126/science.270.5243.1797
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Reports

Efficient Aldolase Catalytic Antibodies That Use the Enamine Mechanism of Natural Enzymes

Jürgen Wagner,  Richard A. Lerner (1),  Carlos F. Barbas III (1)

Antibodies that catalyze the aldol reaction, a basic carbon-carbon bond-forming reaction, have been generated. The mechanism for antibody catalysis of this reaction mimics that used by natural class I aldolase enzymes. Immunization with a reactive compound covalently trapped a Lys residue in the binding pocket of the antibody by formation of a stable vinylogous amide. The reaction mechanism for the formation of the covalent antibody-hapten complex was recruited to catalyze the aldol reaction. The antibodies use the -amino group of Lys to form an enamine with ketone substrates and use this enamine as a nascent carbon nucleophile to attack the second substrate, an aldehyde, to form a new carbon-carbon bond. The antibodies control the diastereofacial selectivity of the reaction in both Cram-Felkin and anti-Cram-Felkin directions.


Departments of Chemistry and Molecular Biology, Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA.
(1) To whom correspondence should be addressed.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)