In the course of synthesizing transition-state analogs for cocaine hydrolysis we have used EI-MS and FAB-MS for characterization of intermediates. Cocaine addiction is reinforced the higher its peak serum concentration and the faster its rate of rise to the peak. I am developing an artificial enzyme which would reduce serum cocaine concentrations, deprive the cocaine abuser of the behavioral reinforcing effect of the drug, and thus favor extinction of the addiction. Catalytic antibodies are artificial enzymes obtained by immunizing animals with an analog of the target molecule that resembles the target in the midst of being torn apart. Cocaine can be degraded by cleaving it at its benzoyl ester group and an analog designed to mimic the shape of cocaine in the midst of this cleaving can be injected into mice and the antibodies that form can act as highly specific enzymes against cocaine. I developed a sensitive, simple procedure for detecting antibodies that not only bind but destroy cocaine and thus far, nine of the antibodies have demonstrated this activity. We have demonstrated the ability of one enzyme to block lethal doses of cocaine in rat. We have cloned the nine catalytic antibodies and site-specific modification of antibodies will be guided by 3-dimensional structure determination of fragments that we have expressed. With the potential to promote cessation of use, prolong abstinence and provide a treatment for acute overdose, the artificial enzyme approach comprehensively responds to the problem of cocaine.
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