Elucidating functional mechanisms for drug resistance in HIV-1 protease

阐明 HIV-1 蛋白酶耐药性的功能机制

• 批准号: 8909393
• 负责人: Thomas M Casey
• 金额: $ 4.03万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-16 至 2016-04-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8909393
• 关键词: Accounting; Acquired Immunodeficiency Syndrome; Active Sites; Address; Affect; Antiviral Agents; Behavior; Binding; Biochemical; Biochemistry; Biological; Biological Assay; Catalysis; Characteristics; Clinical Treatment; Data; Development; Drug Design; Drug resistance; Electron Spin Resonance Spectroscopy; Environment; Enzymes; Epidemic; Equilibrium; Europe; FDA approved; Florida; Frequencies; Funding; Funding Opportunities; Genetic Polymorphism; Goals; HIV; HIV Infections; HIV-1; HIV-1 protease; Hydration status; Individual; Infection; Kinetics; Knowledge; Lead; Link; Measurement; Measures; Mediating; Modeling; Molecular; Molecular Biology; Molecular Conformation; Multi-Drug Resistance; Mutation; Nuclear; Nuclear Magnetic Resonance; Outcome; Pattern; Peptide Hydrolases; Pharmaceutical Preparations; Pharmacotherapy; Physiologic pulse; Population; Preparation; Property; Protease Inhibitor; Protein Dynamics; Proteins; Relative (related person); Relaxation; Research; Research Personnel; Role; Science; Scientist; Series; Spectrum Analysis; Structure; Surgical Flaps; Techniques; Training; Universities; Variant; Viral; Virus; Work; base; career; citizen science; design; enzyme structure; fitness; inhibitor/antagonist; innovation; insight; novel; pressure; public health relevance; treatment strategy

 DESCRIPTION (provided by applicant): This proposal addresses the problem of drug resistance in HIV-1 protease, an enzyme essential to the maturation of HIV infection to Acquired Immunodeficiency Syndrome (AIDS). Unique HIV-1 protease constructs with mutations known to cause drug resistance will be studied using a combination of Electron Paramagnetic Resonance (EPR), Nuclear Magnetic Resonance (NMR), and a host of biochemical and molecular biological analysis techniques. The constructs will be characterized in terms of structural properties, functional properties, enzymatic activity, and drug resistance. The expected outcome is to determine a relationship between enzyme structure, function, activity, and drug resistance that can be used to understand the problem of drug resistance from a functional perspective and aid in devising new strategies for treatment of HIV infection on a global scale. Another major goal of this funding opportunity is to provide a diverse training environment for the funded individual to aid in preparation for a career as a significantly productive independent researcher.

 描述（由应用提供）：该提案解决了HIV-1蛋白酶中耐药性问题，这是HIV感染对获得的免疫缺陷综合征（AIDS）的成熟至关重要的酶。具有电子顺磁共振（EPR），核磁共振（NMR）和许多生化和分子生物学分析技术的组合，将使用已知会引起耐药性的突变的独特HIV-1蛋白酶构建体进行研究。这些结构特性，功能特性，酶活性和耐药性将以构造的特征。预期的结果是确定酶结构，功能，活性和耐药性之间的关系，该关系可用于从功能的角度来理解耐药性问题，并有助于制定新的策略，以在全球范围内治疗HIV感染的新策略。这个资金机会的另一个主要目标是为资助的个人提供潜水员培训环境，以帮助为自己的职业做准备，成为一名生产力更高的独立研究人员。