COCAINE CATALYTIC ANTIBODIES: NOVEL TECHNOLOGY FOR DEMAND REDUCTION

在合成可卡因的过渡态类似物的过程中 水解我们已经使用EI-MS和FAB-MS来表征 中间体的 可卡因成瘾的高峰越高， 血清浓度越高，其上升至峰值的速度越快。 我是 开发一种人造酶， 浓度，剥夺可卡因滥用者的行为， 加强药物的作用，从而有利于灭绝的药物。 成瘾 催化抗体是人工酶， 用靶分子的类似物免疫动物， 看起来像是被撕裂的目标 咖啡可以是 通过在其苯甲酰基酯基团处裂解而降解， 在切割过程中模仿可卡因的形状 可以注射到小鼠体内，形成的抗体可以作为 对可卡因有高度特异性的酶 我培养了一种敏感， 检测抗体的简单方法， 到目前为止，已经有九种抗体证明， 这个活动。 我们已经证明了一种酶能够 阻断大鼠体内可卡因的致死剂量。 我们克隆了九个 催化抗体和抗体的位点特异性修饰将 通过确定碎片的三维结构来指导， 我们已经表达了。 有可能促进停止使用， 延长禁欲期，并提供急性过量的治疗， 人工酶的方法全面回应了这个问题， 可卡因

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.