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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 HIV-1 蛋白酶 (HIV PR) 是一种天冬氨酸蛋白酶，对于 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蛋白，以产生传染性 HIV 病毒粒子的成熟蛋白质成分。如果没有有效的 HIV PR，HIV 病毒粒子仍然不具有传染性。 因此，HIV PR活性位点的突变或对其活性的抑制会破坏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。 对 HIV PR 进行了高场 ESR 研究，以便使用各种流行的自旋标签更好地解析抑制和非抑制形式的 PR 的瓣动态。 在尝试的自旋标签中，MSL 在 240 GHz 下抑制和非抑制形式的 HIV PR 的瓣动力学方面显示出可解决的差异。 在较低频率下，没有一个自旋标签能够解决襟翼动力学差异。 鉴于使用 MSL 的 240 GHz 结果允许人们解析皮瓣动力学的细节，从而充当有效 HIV PR 抑制或非抑制的“指纹”，因此需要对 240 GHz 下的耐药菌株和不同抑制剂进行进一步研究。计划。