Efficient aldolase catalytic antibodies that use the enamine mechanism of natural enzymes.
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.
Wagner
J
J
Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.
Lerner
R A
RA
Barbas
C F
CF
D000096:Acetone / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D017151:Antibodies, Catalytic / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D000918:Antibody Specificity; D002384:Catalysis; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry* / Q000276:immunology; D006241:Haptens / Q000737:chemistry / Q000276:immunology; D008239:Lysine / Q000737:chemistry; D051379:Mice; D013379:Substrate Specificity
D000447:Aldehydes; D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; D006241:Haptens; D000096:Acetone; D005634:Fructose-Bisphosphate Aldolase; D008239:Lysine