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: 8169745
• 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: 2010
• 资助国家: 美国
• 起止时间: 2010-09-12 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169745
• 关键词: Affinity; Binding; Chemicals; Computer Graphics; Computer Retrieval of Information on Scientific Projects Database; Databases; Drug Design; Funding; Goals; Grant; Half-Life; Hepatitis A; Institution; Lead; Ligand Binding; Malaria; Mass Spectrum Analysis; Modeling; Pathogenesis; Peptide Hydrolases; Peptides; Pharmaceutical Chemistry; Play; Proteomics; Research; Research Personnel; Resources; Role; Schistosomiasis; Screening procedure; Source; Specificity; Staging; Structural Models; Structure; Toxic effect; Trypanosomiasis; United States National Institutes of Health; Virus Diseases; base; design; improved; inhibitor/antagonist; mimetics; 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 peptido-mimetic inhibitors, specifically targeted against proteases central to the pathogenesis of malaria, schistosomiasis, trypanosomiasis, and hepatitis A. Crystal structures and in some cases homology-based structural models for target proteases are used for computer-graphics based modeling of ligand binding, for database screening of potential inhibitors as well as for analysis of potential binding modes. Optimization of these compounds is aimed at improving specificity, half-life, and diminishing toxicity. Using medicinal chemistry approaches, we have designed and synthesized a wide variety of chemical compounds which include heteroaromatic inhibitors, peptide-based and peptidomimetic inhibitors. In the early years of this project, mass spectrometry has played an important role in chemical characterization of these lead compounds. Proteomic analysis is also important at early stages of target identification, using affinity based probes that target specific functional subclasses of protease activities.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目的目标是设计和合成新型的肽和肽模拟抑制剂，该抑制剂针对蛋白酶，针对疟疾发病机理，血吸虫病，锥虫病和肝炎A的核心。以及分析潜在结合模式。 这些化合物的优化旨在提高特异性，半衰期和毒性降低。 使用药物化学方法，我们设计并合成了各种化合物，包括杂芳族抑制剂，基于肽的抑制剂和肽型抑制剂。 在该项目的早期，质谱法在这些铅化合物的化学表征中发挥了重要作用。 蛋白质组学分析在目标识别的早期阶段也很重要，使用基于亲和力的探针，这些探针针对蛋白酶活性的特定功能亚类。