Highly Efficient Antibody-Catalyzed Deuteration of Carbonyl Compounds

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 (kcat) and rate‐enhancement values (kcat/kun) 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 16O/18O 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. High regio‐ and chemoselectivity, catalytic rates, and rate‐enhancement values are obtained when the catalytic antibody 38C2 is used to catalyze the deuterium‐exchange reaction at the α position of a wide range of ketones and aldehydes, as shown, even in substrates that have sensitive functional groups.