École Polytechnique Fédérale de Lausanne, Institute of Chemical Sciences and Engineering, 1015 Lausanne, Switzerland; Cornell University, Ithaca, NY 14850, USA.
47 Pudding Gate, Bishop Burton, Beverley, HU17 8QH, UK.
Trends Biochem Sci. 2019 Apr;44(4):380-381. doi: 10.1016/j.tibs.2019.01.006. Epub 2019 Feb 11.
Understanding the targets and signaling roles of reactive electrophilic species (RES) at a specific cellular space and time has long been hampered by the reliance of the field on the bulk administration of excess RES from outside of cells and/or animals. Uncontrolled bolus methods provide limited understanding of target engagement for these individual nonenzymatic RES-modification events. REX technologies [targetable reactive electrophiles and oxidants (T-REX) and its genome-wide variant (G-REX)] were developed as a gateway to address these limitations. These protocols offer a new ability to both profile kinetically privileged sensors (KPSs) of RES at a systems level (G-REX™ profiling) and monitor signaling responses at the sensor protein-of-interest (POI)-specific level (T-REX™ delivery) with high spatiotemporal resolution. REX technologies are compatible with several model systems and are built on a HaloTag-targetable small-molecule photocaged precursor to a native RES.
长期以来，由于该领域依赖于从细胞外和/或动物体过量给予反应性亲电物质（RES），因此在特定细胞空间和时间理解反应性亲电物质的靶标和信号作用一直受到阻碍。不受控制的推注方法对这些非酶促 RES 修饰事件的靶标结合提供了有限的了解。REX 技术 [靶向反应性亲电物质和氧化剂 (T-REX) 及其全基因组变体 (G-REX)] 的开发是解决这些限制的一种途径。这些方案提供了一种新的能力，可以在系统水平上对 RES 的动力学优先传感器 (KPS) 进行分析（G-REX™ 分析），并以高时空分辨率监测传感器蛋白（POI）特异性水平的信号响应（T-REX™ 传递）。REX 技术与几种模型系统兼容，并基于可靶向 HaloTag 的小分子光笼前体构建，该前体是天然 RES。
