DESIGN AND ORGANIC SYNTHESIS OF INHIBITORS OF FIV PROTEASE

这项研究将开发合理的方法来设计和综合 猫免疫缺陷天冬氨酸蛋白酶抑制剂的研究进展 病毒(FIV)和人类免疫缺陷病毒(HIV-1)。会的 重点关注以下计划： 1.开发高效高亲和力小肽底物 包含一个基于周围序列的剪刀式Tyr-Pro键 FIV蛋白水解酶的切割位点。 2.探讨人工合成FIV蛋白酶的反应机理。 底物。 3.设计合成酪氨酸-Pro多肽的同工酶和过渡态 类似的抑制剂，或基于其机制的灭活剂 FIV和HIV酶催化的切割反应。 4.使用计算机辅助和基于机制的合理药物设计周期 提高抑制剂的效力；加入额外的多肽 或与抑制剂的非肽互补成分。 5.开发新的化学方法来合成蛋白酶抑制剂。 一般的，特别是天冬氨酸蛋白酶。 在生物医学、药物设计和 预计会有合成有机化学专业。这些发展将 促进发现和开发新的治疗药物 艾滋病。

This research will develop rational approaches to the design and synthesis of inhibitors of the aspartyl protease from the feline immunodeficiency virus (FIV) and from the human immunodeficiency virus (HIV-1). It will focus on the following programs: 1. Develop effective and high-affinity small peptide substrates containing a scissle Tyr-Pro bond based on the sequences around the cleavage sites of FIV protease. 2. Investigate the mechanism of FIV protease reaction with synthetic substrates. 3. Design and synthesize Tyr-Pro peptide isostere and transition state analog inhibitors, or mechanism-based inactivators based on its cleavage reaction catalyzed by FIV and HIV protease. 4. Use computer-assisted and mechanism-based rational drug design cycles to improve the potency of inhibitors; incorporate additional peptide or nonpeptide complementarity components to the inhibitors. 5. Develop new chemistry for the synthesis of protease inhibitors in general and aspartyl proteases in particular. Significant contributions in the areas of biomedicine, drug design, and synthetic organic chemistry are expected. These developments will facilitate the discovery and development of new therapeutic agents for AIDS.