关键词: Azobenzene Deuteration G Protein-Coupled Receptor Ion Channel Photopharmacology

来  源:   DOI:10.1002/anie.202408300

Abstract:
Chemical photoswitches have become a widely used approach for the remote control of biological functions with spatiotemporal precision. Several molecular scaffolds have been implemented to improve photoswitch characteristics, ranging from the nature of the photoswitch itself (e.g. azobenzenes, dithienylethenes, hemithioindigo) to fine-tuning of aromatic units and substituents. Herein, we present deuterated azobenzene photoswitches as a general means of enhancing the performance of photopharmacological molecules. Deuteration can improve azobenzene performance in terms of light sensitivity (higher molar extinction coefficient), photoswitch efficiency (higher photoisomerization quantum yield), and photoswitch kinetics (faster macroscopic rate of photoisomerization) with minimal alteration to the underlying structure of the photopharmacological ligand. We report synthesized deuterated azobenzene-based ligands for the optimized optical control of ion channel and G protein-coupled receptor (GPCR) function in live cells, setting the stage for the straightforward, widespread adoption of this approach.
摘要:
化学光开关已成为一种广泛使用的方法,用于以时空精度远程控制生物功能。已经实施了几种分子支架来改善光开关特性,从光电开关本身的性质(例如偶氮苯,二噻吩乙烯,半硫代靛蓝)对芳族单元和取代基进行微调。在这里,我们提出了氘代偶氮苯光开关作为增强光药理学分子性能的一般手段。氘代可以提高偶氮苯在光敏性方面的性能(更高的摩尔消光系数),光开关效率(更高的光异构化量子产率),和光开关动力学(更快的宏观光异构化速率),对光药理学配体的基础结构的改变最小。我们报告了合成的基于氘代偶氮苯的配体,用于优化活细胞中离子通道和G蛋白偶联受体(GPCR)功能的光学控制,为直截了当的人搭建舞台,广泛采用这种方法。
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