Presidential Young Investigator Award/Catalytic Antibodies

本研究的重点是调查新的 催化剂的设计和生产方法 抗体的一般来说，抗体产生的化合物， 期望类似于所需反应的过渡态 利用束缚力来降低真实的跃迁的能量 在类似的化学转化中。催化速率 增强高达一百万倍以上的背景， 使用这种策略。精美基材 特异性，适当时包括立体特异性， 这种特异性可以被编程为 该抗体由原免疫原的结构 半抗原。有三个主要项目， 利用这种催化抗体的可编程特异性。 在每种情况下，用于产生抗肿瘤抗体的标准杂交瘤技术都是可行的。 新分子生物学增强小鼠单克隆抗体 方法将被使用。第一个项目将探讨使用 催化抗体来操纵化学保护基团 在有机合成中。第二个项目涉及测试 金属辅因子在抗体催化反应中的应用。 第三个项目旨在建立一个基于抗体的系统 它可以重现 光合作用 %%% 有了这个总统青年研究者奖，合成 化学部的有机计划将支持 化学系布伦特·艾弗森博士的研究 德克萨斯大学奥斯汀分校的生物化学， 催化抗体这些抗体是通过挑战 小鼠的免疫系统与化合物类似高 所需反应的能量或过渡态，通常 能够提供高至 一百万倍因此，这些抗体类似于 是催化蛋白质，但其功能是催化反应， 没有酶存在。

The focus of this research is the investigation of new approaches for the design and production of catalytic antibodies. In general, antibodies raised to compounds that resemble transition states of a desired reaction are expected to use binding forces to lower the energy of a real transition state in the analogous chemical transformation. Catalytic rate enhancements as high as one million-fold over background have been observed using this strategy. Exquisite substrate specificity, including stereospecificity when appropriate, is always observed, and this specificity can be programmed into the antibody by the structure of the original immunizing haptens. There are three major projects, all designed to exploit this programmable specificity of catalytic antibodies. In each case, standard hybridoma techniques for production of monoclonal antibodies in mice enhanced by new molecular biology methods will be used. The first project will probe the use of catalytic antibodies to manipulate chemical protecting groups during organic synthesis. The second project involves testing the utility of metal cofactors in antibody catalyzed reactions. The third project seeks to generate an antibody-based system that can reproduce some of the essential features of photosynthesis. %%% With this Presidential Young Investigator Award, the Synthetic Organic Program of the Chemistry Division will support the research of Dr. Brent Iverson of the Department of Chemistry and Biochemistry at the University of Texas at Austin on catalytic antibodies. These antibodies, produced by challenging the immune systems of mice with compounds that resemble high energy or transition states of desired reactions, frequently are capable of providing catalytic rate enhancements as high as one million-fold. Thus these antibodies resemble enzymes in being catalytic proteins, but function to catalyze reactions for which no enzymes exist.