SYNTHESIS, ENZYMOLOGY, AND DRUG DESIGN

合成、酶学和药物设计部分受到 保罗·奥尔蒂斯·德·蒙特拉诺博士和乔治·凯尼恩博士的研究小组。 这两个小组带来了合成、机械、 酶学和药物化学的合作努力和 负责所有化合物的合成 在该计划项目中进行评估。这两个小组都有具体的 计划项目中的职责和感兴趣的领域： 奥尔蒂斯·德·蒙特拉诺博士负责所有化学方面的 关于艾滋病毒蛋白水解酶的工作，以及肯扬博士对艾滋病毒研究的工作 逆转录酶和核糖核酸酶H，并用于开发新的 反义核酸低聚物的构建技术。 此外，合成体的责任很可能是 基团将随着其他HIV蛋白的晶体结构而扩大 (例如，整合酶)变得可用，使它们成为 合理设计抗HIV药物。 这两个合成小组将合作进行计算， 建模，以及结晶学小组在新开发中的应用 酶抑制剂和酶抑制剂的设计和构造方法 DNA/RNA靶向制剂。一旦候选代理由以下内容定义 方法，他们将负责其化学合成。在……里面 此外，奥尔蒂斯·德·蒙特拉诺集团将提供化学援助 并将与其合作，以澄清 不可逆HIV蛋白酶抑制剂的作用机制。《凯尼恩》 该小组将负责DNA/RNA领域的生物检测，并将 与几个小组合作评估生物活动 核苷酸类似物。 尽管这两个合成小组有不同的研究计划和 在责任方面，这两个群体之间有很强的互动。 S推动的这种互动不仅是由他们共同的兴趣推动的 抗艾滋病毒药物的发展，也是因为他们的 实验室彼此毗邻，并包括一个共享的实验室 太空。这种相互作用增加了化学专业知识， 用来解决合成问题。 奥尔蒂斯·德·蒙特拉诺和凯尼恩小组的详细研究计划 在接下来的几页中分别以不同的部分介绍。

The synthesis, Enzymology, and Drug Design section is compromised of the research groups of Drs. Paul Ortiz de Montellano and George Kenyon. These two groups bring expertise in synthetic, mechanistic, enzymological, and medicinal chemistry to the collaborative effort and are responsible for the synthesis of all the compounds that are to be evaluated in this program project. The two groups have specific responsibilities and areas of interest within the program project: that of Dr. Ortiz de montellano is responsible for all chemical aspects of the work on HIV proteases, and that of Dr. Kenyon for studies of the HIV reverse transcriptase and ribonuclease H, and for the development of new technologies for the construction of antisense nucleic acid oligomers. It is likely, furthermore, that the responsibilities of the synthetic groups will expand as the crystal structures of other HIV proteins (e.g., integrase) become available, making them viable targets for the rational design of anti-HIV agents. The two synthetic groups will collaborate with the computation, modeling, and crystallography groups in the development of new approaches for the design and construction of enzyme inhibitors and DNA/RNA targeted agents. Once a candidate agent is defined by these methods, they will be responsible for its chemical synthesis. In addition, the Ortiz de Montellano group will provide chemical assistance to the bioassay group and will collaborate with it in elucidating the mechanisms of action of irreversible HIV protease inhibitors. The Kenyon group will be responsible for bioassays in the DNA/RNA area and will collaborate with several groups in evaluating the biological activities of nucleotide analogues. Although the two synthetic groups have distinct research plans and responsibilities, there is a strong interaction between the two groups. This interaction s promoted not only by their common interest in the development of anti-HIV agents, but also by the fact that their laboratories are adjacent to each other and include a shared laboratory space. This interaction increases the chemical expertise that can be brought to bear to resolve synthetic problems. The detailed research plans of the Ortiz de Montellano and Kenyon groups are presented in separate sections in the following pages.