A Biochemical/Biophysical Assay Dyad for HTS-Compatible Triaging of Inhibitors of the HIV-1 Nef/Hck SH3 Interaction.

Sebastian Breuer, Sheryll Espinola, Xavier Morelli, Bruce E Torbett, Stefan T Arold, Ingo H Engels
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引用次数: 3

Abstract

The current treatment regimens for HIV include over 20 anti-retrovirals. However, adverse drug effects and the emergence of drug resistance necessitates the continued improvement of the existing drug classes as well as the development of novel drugs that target as yet therapeutically unexploited viral and cellular pathways. Here we demonstrate a strategy for the discovery of protein-protein interaction inhibitors of the viral pathogenicity factor HIV-1 Nef and its interaction with the host factor SH3. A combination of a time-resolved fluorescence resonance energy resonance energy transfer-based assay and a label-free resonant waveguide grating-based assay was optimized for high-throughput screening formats.

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hts兼容筛选HIV-1 Nef/Hck SH3相互作用抑制剂的生化/生物物理检测方法
目前的艾滋病治疗方案包括20多种抗逆转录病毒药物。然而,药物的副作用和耐药性的出现需要不断改进现有的药物类别,以及开发针对尚未治疗的病毒和细胞途径的新型药物。在这里,我们展示了一种发现病毒致病性因子HIV-1 Nef及其与宿主因子SH3相互作用的蛋白-蛋白相互作用抑制剂的策略。基于时间分辨荧光共振能量共振能量转移的检测方法和基于无标记共振波导光栅的检测方法的组合被优化为高通量筛选格式。
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