HIGH FIELD ESR STUDIES ON HIV-1 PROTEASE

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 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。

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. 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.