HIGH FIELD ESR STUDIES ON HIV-1 PROTEASE

HIV-1 蛋白酶的高场 ESR 研究

• 批准号: 8364010
• 负责人: KEITH A EARLE
• 金额: $ 1.76万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364010
• 关键词: Active Sites; Aspartic Endopeptidases; Cells; Cleaved cell; Drug resistance; Fingerprint; Frequencies; Funding; Grant; HIV; HIV Protease; HIV-1; Life Cycle Stages; Mutation; National Center for Research Resources; Peptide Hydrolases; Pharmacologic Substance; Polyproteins; Principal Investigator; Proteins; Research; Research Infrastructure; Resolution; Resources; Source; Spin Labels; Surgical Flaps; Technology; United States National Institutes of Health; Virion; cost; inhibitor/antagonist; resistant strain

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. HIV-1 protease (HIV PR) is an aspartic protease that is essential for the life-cycle of HIV. HIV PR cleaves newly synthesized polyproteins at the appropriate places to create the mature protein components of an infectious HIV virion. Without effective HIV PR, HIV virions remain uninfectious. Thus, mutation of HIV PR's active site or inhibition of its activity disrupts HIV's ability to replicate and infect additional cells, making HIV PR inhibition the subject of much pharmaceutical research. High Field ESR studies were undertaken of HIV PR in order to better resolve flap dynamics of the PR in inhibited and non-inhibited forms, using a variety of popular spin labels. Of the spin labels tried, MSL showed resolvable differences in the flap dynamics of inhibited and non-inhibited forms of HIV PR at 240 GHz. At lower frequencies, none of the spin labels allowed resolution of a difference in flap dynamics. Given that the 240 GHz results using MSL allow one to resolve details of the flap dynamics, and thus act as a 'fingerprint' for effective HIV PR inhibition or non-inhibition, further studies on drug-resistant strains and different inhibitors at 240 GHz are planned.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 HIV-1蛋白酶（HIV PR）是一种天冬氨酸蛋白酶，对HIV的生命周期至关重要。HIV PR在适当的位置切割新合成的多聚蛋白，以产生感染性HIV病毒体的成熟蛋白组分。如果没有有效的HIV PR，HIV病毒体仍然没有传染性。 因此，HIV PR活性位点的突变或其活性的抑制破坏了HIV复制和感染其他细胞的能力，使得HIV PR抑制成为许多药物研究的主题。 进行HIV PR的高场ESR研究，以便使用各种流行的自旋标记更好地解析PR在抑制和非抑制形式下的瓣动力学。 自旋标签尝试，MSL显示出可分辨的差异，在皮瓣动力学的抑制和非抑制形式的HIV PR在240 GHz。 在较低的频率下，没有一个自旋标签允许襟翼动力学差异的分辨率。 考虑到使用MSL的240 GHz结果允许解析皮瓣动力学的细节，从而作为有效HIV PR抑制或非抑制的“指纹”，计划在240 GHz下对耐药菌株和不同抑制剂进行进一步研究。