STRUCTURE BASED DRUG DESIGN FOR TREATMENT OF PARASITIC AND VIRAL DISEASES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们的目标是设计和合成新的多肽和模拟肽抑制剂，专门针对疟疾、血吸虫病和甲型肝炎发病机制中的关键酶，在缺乏我们感兴趣的半胱氨酸蛋白酶的X射线结构的情况下，我们模拟了基于与其他半胱氨酸蛋白酶序列同源性的酶模型。我们设计和合成了多种化合物，包括杂芳烃抑制剂、多肽类和模拟多肽类抑制剂。质谱学与核磁共振谱、核磁共振谱等一起，在表征这些具有不同化学性质和背景的先导化合物方面发挥了重要作用。质谱学仍将是我们分析下一代抑制剂研究中不可或缺的一部分。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our goal for this project is to design and synthesize novel peptide and peptidomimetic inhibitors, specifically targeted against proteases central to the pathogenesis of malaria, schistosomiasis and hepatitis A. In the absence of X-ray structure of cysteine protease of our interest, we have simulated the enzyme model based on sequence homology to other cysteine proteases. We have designed and synthesized a wide variety of chemical compounds which include heteroaromatic inhibitors, peptide-based and peptidomimetic inhibitors. Mass spectrometry has played an important role in association with 1NMR, 13C NMR, 19F NMR and 31P NMR in characterizing these lead compounds of diverse chemical nature and background. Mass Spectrometry will remain an integral part of our research in analyzing the next generation of inhibitors.