STRUCTURE BASED DRUG DESIGN FOR TREATMENT OF PARASITIC AND VIRAL DISEASES

用于治疗寄生虫和病毒性疾病的基于结构的药物设计

• 批准号: 7957385
• 负责人: James H. McKerrow
• 金额: $ 0.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957385
• 关键词: Chemicals; Computer Retrieval of Information on Scientific Projects Database; Cysteine Protease; Drug Design; Funding; Goals; Grant; Hepatitis A; Institution; Lead; Malaria; Mass Spectrum Analysis; Nature; Pathogenesis; Peptide Hydrolases; Peptides; Play; Research; Research Personnel; Resources; Roentgen Rays; Role; Schistosomiasis; Sequence Homology; Simulate; Source; Structure; United States National Institutes of Health; Virus Diseases; base; design; enzyme model; inhibitor/antagonist; interest; next generation; novel; peptidomimetics

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本项目的目标是设计和合成新型肽和拟肽抑制剂，特异性靶向于疟疾、血吸虫病和甲型肝炎发病机制的蛋白酶。在没有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的序列同源性的酶模型。我们已经设计并合成了各种各样的化合物，其中包括杂环抑制剂，肽基和拟肽抑制剂。质谱联用1 NMR、13 C NMR、19 F NMR和31 P NMR在表征这些具有不同化学性质和背景的先导化合物中发挥了重要作用。质谱分析将仍然是我们分析下一代抑制剂研究的一个组成部分。