HIGH FIELD ESR STUDIES ON HIV-1 PROTEASE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级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，在HIV的生命周期中起着至关重要的作用。HIV PR在适当的位置裂解新合成的多蛋白，以产生具有感染性的HIV病毒粒子的成熟蛋白质成分。如果没有有效的艾滋病毒公关，艾滋病毒病毒粒子仍然不具传染性。因此，HIV PR活性部位的突变或其活性的抑制会破坏HIV复制和感染额外细胞的能力，使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，以更好地解决PR在抑制和非抑制形式下的翻盖动力学，使用了各种流行的自旋标签。在所尝试的自旋标记中，MSL显示出在240 GHz处抑制形式和非抑制形式的HIV PR的翻盖动力学上的可解决的差异。在较低的频率下，没有一个自旋标记允许分辨襟翼动力学上的差异。考虑到使用MSL的240 GHz结果允许人们解析翻盖动力学的细节，从而作为有效的HIV PR抑制或非抑制的“指纹”，计划在240 GHz对耐药菌株和不同的抑制剂进行进一步的研究。

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.