DESIGN AND ORGANIC SYNTHESIS OF INHIBITORS OF FIV PROTEASE

本研究将发展合理的设计和合成方法 猫免疫缺陷病毒的乙酰基蛋白酶抑制剂 病毒（FIV）和人类免疫缺陷病毒（HIV-1）。 它将 重点开展以下方案： 1. 开发高效、高亲和力的小肽底物 含有一个scissle Tyr-Pro键，基于 FIV蛋白酶的切割位点。 2. 研究FIV蛋白酶与合成的 印刷受体. 3. Tyr-Pro肽电子等排体及过渡态的设计与合成 类似物抑制剂，或基于其 FIV和HIV蛋白酶催化的裂解反应。 4. 使用计算机辅助和基于机理的合理药物设计周期 以提高抑制剂的效力;掺入额外的肽 或与抑制剂互补的非肽组分。 5. 开发新的化学合成蛋白酶抑制剂， 一般蛋白酶，特别是乙酰基蛋白酶。 在生物医学、药物设计和 合成有机化学。 这些发展将 促进新治疗剂的发现和开发， 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.