Cocaine-hydrolyzing antibody

Powerful selective antidotes or antagonists to treat cocaine abuse are necessary to offset the increased cocaine toxicity currently observed in the United States. The use of catalytic antibodies in the creation of selective binding agents and detoxication catalysts of cocaine could represent a novel approach that may result in significant advances in the field of detoxication of drugs of abuse. An anti-cocaine catalytic antibody directed to hydrolyze the benzoyl ester could in principle catalyze the formation of ecgonine and benzoic acid, hydrolysis products of cocaine that do not possess the reinforcing or CNS stimulation properties of cocaine (Spealman et al. 1989). 

Cashman JR, Berkman CE, Underiner GE. Catalytic antibodies that hydrolyze (—)-cocaine obtained by a high-throughput procedure. J. Pharmacol. Exp. Ther. 2000 293(3) 952-961. 

Typical antibody-catalyzed reaction rates are several hundredfold to 100,000-fold faster than the uncatalyzed reaction of the substrate. Several fundamental postulates have been proposed to explain the rate enhancements that nevertheless fall short of the enormous rate accelerations of enzymes. Is activity truly due solely to transition state stabilization by antibody-binding interactions Can additional binding interactions be built into the combining site or into the substrate molecule itself to increase the overall rate of the reaction Can new screening methods and immunological methods be developed to uncover novel catalysts with diverse activities Most important, can novel esterolytic catalysts be developed based on currently available catalytic antibody technology to efficiently hydrolyze and detoxicate cocaine ... 

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