189361-75-9Relevant articles and documents
Design and Synthesis of Transition State Analogs for Induction of Hydride Transfer Catalytic Antibodies
Schroeer, Josef,Sanner, Michel,Reymond, Jean-Louis,Lerner, Richard A.
, p. 3220 - 3229 (1997)
Alcohol dehydrogenases and related aldehyde reductase enzymes catalyze the oxidation of alcohols to aldehydes and the simultaneous reduction of a nicotinamide derivative (NAD+ or NADP+) to the corresponding 1,4-dihydronicotinamide.Herien we report the design and synthesis of a stable transition state analog for this hydride transfer process.Compound 1 is a rigid bicyclic structire containing 3-piperidone oxime as a mimic for 1,4-dihydronicotinamide.The piperidone is held in the boat conformation corresponding to the transition state by a three-atom lactam bridge between N(1) and C(4).The oxime function mimics the carboxamide group in nicotinamide.The lactam nitrogen serves as an attachment point for the alkyl group of the alcohol substrate , and the amide oxygen atom mimics its hydroxyl group.Compound 1 was prepared in in 10 steps from N-benzylpiperidone, functionalized with substrate and cofactor recognition elements into transition state analogs 2 and 3 and conjugated to carrier proteins for immunization.These novel analogs open the way for the exploration of the dehydrogenase reaction using catalytic antibodies.
