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Highly Efficient Antibody‐Catalyzed Deuteration of Carbonyl Compounds
Author(s) -
Shulman Avidor,
Sitry Danielle,
Shulman Hagit,
Keinan Ehud
Publication year - 2002
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20020104)8:1<229::aid-chem229>3.0.co;2-p
Subject(s) - chemistry , catalysis , aldolase a , aldol reaction , enamine , enzyme kinetics , substrate (aquarium) , chemoselectivity , ketone , stereochemistry , combinatorial chemistry , enzyme , organic chemistry , active site , biology , ecology
Antibody 38C2 efficiently catalyzes deuterium‐exchange reactions at the α position of a variety of ketones and aldehydes, including substrates that have a variety of sensitive functional groups. In addition to the regio‐ and chemoselectivity of these reactions, the catalytic rates ( k cat ) and rate‐enhancement values ( k cat / k un ) are among the highest values ever observed with catalytic antibodies. Comparison of the substrate range of the catalytic antibody with highly evolved aldolase enzymes, such as rabbit‐muscle aldolase, highlights the much broader practical scope of the antibody, which accepts a wide range of substrates. The hydrogen‐exchange reaction was used for calibration and mapping of the antibody active site. Isotope‐exchange experiments with cycloheptanone reveal that the formation of the Schiff base species (as concluded from the 16 O/ 18 O exchange rate at the carbonyl oxygen) is much faster than the formation of the enamine intermediate (as concluded from the H/D exchange rate), and both steps are faster than the antibody‐catalyzed aldol addition reaction.