Anti-Cocaine Catalytic Antibodies

Abstract

Over 50,000,000 Americans have used cocaine (1) since 1980 and approximately 2,000,000 are presently addicted with disastrous medical and social consequences.¹ At present, no efficient drug therapy is available for the management of cocaine abuse and dependence. Cocaine is hypothesized to exert its addictive effect by blocking a transport protein for the neurotransmitter dopamine, and the difficulties inherent in blocking a blocker may in part explain the failure to develop a useful therapeutic agent. One alternative to the classical receptor antagonist approach would be a circulating catalytic antibody that could degrade cocaine and interfere with the delivery of the drug to the central nervous system. To obtain antibodies able to catalyze the hydrolysis of cocaine to the inactive products, ecgonine methyl ester (2) and benzoic acid (3), we synthesized a series of stable phosphonate monoester transition state analogs for benzoyl esterolysis (4a-c). With these immunogens we elicited the first artificial enzymes able to degrade cocaine in vitro.^2.3