US EPA

2983808 

Journal Article 

Efficient aldolase catalytic antibodies that use the enamine mechanism of natural enzymes 

Wagner, J; Lerner, RA; Barbas, CF 

1995 

1 

Science
ISSN: 0036-8075
EISSN: 1095-9203 

270 

5243 

1797-1800 

English 

8525368 

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 epsilon-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.