STRUCTURE BASED DRUG DESIGN FOR TREATMENT OF PARASITIC AND VIRAL DISEASES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。我们的目标是设计和合成新的肽和拟肽抑制剂，专门针对疟疾、血吸虫病和甲型肝炎发病机制的核心蛋白酶。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，我们基于与其他半胱氨酸蛋白酶的序列同源性模拟了酶模型。我们已经设计和合成了各种各样的化合物，包括杂芳香抑制剂，肽类和拟肽类抑制剂。质谱法与1NMR， 13C NMR， 19F NMR和31P NMR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。质谱法仍将是我们研究分析下一代抑制剂的一个组成部分。

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.