MECHANISTIC STUDY OF RADICALS IN BIOLOGY CATALYSIS

生命，是科学研究范围内最复杂、最迷人的现象。 人，可以定义为简单的功能集成 结构本身缺乏所有的特征， 生活系统我相信详细了解生命过程 包括精确定位功能如何从结构中产生。我决定 成为一名院士，致力于生物有机的研究 化学反应了这种关注，因为它将使我能够探索 生物大分子的结构和相互作用，这样做， 为进一步研究它们的功能提供了基础， 单位和更复杂系统的成员。本提案概述了 旨在研究一些重要酶的实验，这些酶的机制可能 涉及自由基中间体的形成。第一个系统是 研究了3，6-二脱氧己糖的生物合成。我们的重点将 C-3脱氧的机制研究，导致 形成作为重要的免疫显性糖的蛔虫糖。的 第二个要检测的系统是通用酰基辅酶A脱氢酶， 催化脂肪酸β-氧化的第一步。我们最初 我们将致力于研究这种酶的失活， （亚甲基环丙基）乙酰辅酶A，这是牙买加的病原体 呕吐病这些研究的长期目标是建立一个 这些酶过程的功能作为一个完整的理解， 合理设计控制和模拟其 生理作用。然而，对酶机制的研究代表了 只是我研究兴趣的一部分其他一些领域，特别是 半合成酶的设计，衰老的分子基础， 免疫反应的化学机制，引起了我的注意， 是我将来想研究的研究问题。是 我希望我选择的研究领域和研究结果 它将促进化学知识的发展，并在以下领域得到应用： 医学和/或农业。因为我的研究正转向攻击更多 这些基本而困难的问题， 关注和自我教育，研究职业发展奖 在这个时候会在一个关键时刻。它能让我完全 集中精力在自己的工作和监督的努力， 我的同事，也给自由花时间在其他实验室 学习不同的技术和观点， 对新的研究领域产生影响。根据主席的协议，我教假发 每年有一个季度。这次教学活动将使我充分 参与部门的流程，并将有助于保持形象 这是研究生寻找研究顾问的必要条件。 因此，研究职业发展奖将使一个真实的差异， 通过允许最大限度地集中精力进行研究，这是必要的， 为了成熟成为一个生产力和既定的调查员。

Life, the most complex and fascinating phenomenon within the purview of man, may be defined in terms of the functional integration of simple structures that are themselves devoid of all of the characteristics of living systems. I believe that understanding the life process in detail involves pinpointing how function arises from structure. My decision to become an academician and to devote myself to the study of bioorganic chemistry reflects this concern in that it will allow me to probe the structures and interactions of biological macro-molecules, and in so doing, provide the basis for further study of their functions both as discrete units and as members of more complex systems. Outlined in this proposal are experiments designed to study a few important enzymes whose mechanism may involve the formation of a radical intermediate. The first system to be investigated is the biosynthesis of 3,6-dideoxyhexoses. Our emphasis will be placed on the mechanistic studies of C-3 deoxygenation leading to the formation of ascarylose which is an important immuno-dominant sugar. The second system to be examined is general acyl-CoA dehydrogenase which catalyzes the first step of beta-oxidation of fatty acids. Our initial effort will be directed toward studying the inactivation of this enzyme by (methylenecyclopropyl)acetyl-CoA which is the causative agent of Jamaican vomiting sickness. The longterm goal of these studies is to establish a complete understanding of the functions of these enzymatic processes as a prerequisite to the rational design of methods to control and mimic their physiological roles. However, studies of enzymatic mechanisms represent only part of my research interests. A number of other areas, especially the design of semi-synthetic enzymes, the molecular basis of aging and the chemical mechanisms of the immune response, have attracted my attention and are research problems that I would like to investigate in the future. It is my hope that the areas chosen for my research and the results yielded from it will advance chemical knowledge, and have applications in the fields of medicine and/or agriculture. Since my research is moving on to attack more fundamental and difficult problems that will require much of me in the way of attention and self-education, a Research Career Development Award given at this time would come at a critical juncture. It will allow me to fully concentrate on working at the bench myself and supervising the efforts of my coworkers, and also give the freedom to spend time in other laboratories to learn different techniques and perspectives which can be brought back to bear on new areas of inquiry. By agreement with the Chairman, I wig teach for one quarter each year. This teaching activity will keep me sufficiently involved in the flow of the Department, and will help maintain the profile necessary to interest graduate students who are seeking a research advisor. Thus, a Research Career Development Award would make a real difference for me by allowing maximum concentration on research, which is necessary in order to mature into a productive and established investigator.