SYNTHESIS, ENZYMOLOGY, AND DRUG DESIGN

合成，酶学和药物设计部分是妥协的， 保罗·奥尔蒂斯·德蒙泰拉诺和乔治·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， 负责所有化合物的合成 在这个项目中进行评估。这两个团体有具体的 项目中的责任和兴趣领域： 奥尔蒂斯·德蒙泰拉诺博士负责所有化学方面的 艾滋病毒蛋白酶的工作，以及凯尼恩博士对艾滋病毒的研究， 逆转录酶和核糖核酸酶H，并用于开发新的 用于构建反义核酸寡聚体的技术。 此外，合成人的责任很可能是 随着其他HIV蛋白质的晶体结构， (e.g.,整合酶）变得可用，使它们成为 合理设计抗艾滋病毒药物。 两个合成小组将合作进行计算， 模型，和晶体学小组在新的发展， 设计和构建酶抑制剂的方法， DNA/RNA靶向剂。一旦候选代理由这些定义， 方法，他们将负责其化学合成。在 此外，奥尔蒂斯·德蒙泰拉诺集团将提供化学援助 生物测定组，并将与它合作，阐明 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领域的生物测定， 与几个小组合作评估生物活性 核苷酸类似物。 虽然这两个合成组有不同的研究计划， 在责任方面，两个小组之间有很强的互动。 这种互动不仅是因为他们对世界的共同兴趣， 开发抗艾滋病毒药物，而且事实上， 实验室彼此相邻，包括一个共享实验室 空间这种相互作用增加了化学专业知识， 来解决合成问题。 奥尔蒂斯·德蒙泰拉诺和凯尼恩小组的详细研究计划 将在以下各页的单独章节中介绍。

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.