COCAINE CATALYTIC ANTIBODIES: NOVEL TECHNOLOGY FOR DEMAND REDUCTION

可卡因催化抗体：减少需求的新技术

• 批准号: 6258830
• 负责人: DONALD W LANDRY
• 金额: $ 0.03万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6258830
• 关键词: animal tissue; biological products; biomedical resource; proteins; reproductive system

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.

在合成可卡因过渡态类似物的过程中 我们使用 EI-MS 和 FAB-MS 来表征水解 中间体。 可卡因成瘾程度越高，峰值越高 血清浓度越快，其上升至峰值的速度越快。 我是 开发一种可以减少血清可卡因的人工酶 浓度，剥夺可卡因滥用者的行为 增强药物的作用，从而有利于消灭 瘾。 催化抗体是通过以下方法获得的人工酶 用目标分子的类似物对动物进行免疫接种 类似于正在被撕裂的目标。 可卡因可以 通过在苯甲酰酯基团和类似物处裂解而降解 旨在模仿可卡因在分裂过程中的形状 可以注射到小鼠体内，形成的抗体可以充当 针对可卡因的高度特异性酶。 我养成了敏感的、 检测抗体的简单程序不仅结合而且 摧毁可卡因，到目前为止，九种抗体已证明 这项活动。 我们已经证明了一种酶的能力 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 以片段的 3 维结构确定为指导 我们已经表达了。 具有促进停止使用的潜力， 延长戒断时间并治疗急性药物过量， 人工酶方法全面应对 可卡因。