Sanger's Reagent Sensitized Photocleavage of Amide Bond for Constructing Photocages and Regulation of Biological Functions,Journal of the American Chemical Society

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Sanger's Reagent Sensitized Photocleavage of Amide Bond for Constructing Photocages and Regulation of Biological Functions
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2020-02-05 , DOI: 10.1021/jacs.9b11357
Tingwen Wei ₁ , Sheng Lu ₁ , Jiahui Sun _{2,

3} , Zhijun Xu ₁ , Xiao Yang ₁ , Fang Wang ₁ , Yang Ma ₁ , Yun Stone Shi _{2,

3,

4} , Xiaoqiang Chen ₁

Affiliation

Photolabile groups offer promising tools to study biological processes with highly spatial and temporal control. In the investigation, we designed and prepared several new glycine amide derivatives of Sanger's reagent and demonstrated that they serve as a new class of photocages for Zn2+ and an acetylcholinesterase (AChE) inhibitor. We showed that the mechanism for photocleavage of these substances involves initial light-driven cyclization between the 2,4-dinitrophenyl and glycine methylene groups to form acyl benzimidazole N-oxides, which undergo secondary photoinduced decarboxylation in association with rupture of an amide bond. The cleavage reactions proceed with modest to high quantum yields. We demonstrated that these derivatives can be used in targeted intracellular delivery of Zn2+, fluorescent imaging by light-triggered Zn2+ release, and regulation of biological processes including the enzymatic activity of carbonic anhydrase (CA), negative regulation of N-methyl-D-aspartate receptors (NMDARs) and pulse rate of cardiomyocytes. The successful proof-of-concept examples described above open a new avenue for using Sanger's reagent-based glycine amides as photocages for the exploration of complex cellular functions and signaling pathways.

中文翻译：

用于构建光笼和调节生物功能的 Sanger 试剂敏化酰胺键的光裂解

光不稳定群体提供了有前途的工具来研究具有高度空间和时间控制的生物过程。在研究中，我们设计并制备了 Sanger 试剂的几种新型甘氨酸酰胺衍生物，并证明它们可用作 Zn2+ 和乙酰胆碱酯酶 (AChE) 抑制剂的一类新型光笼。我们表明，这些物质的光裂解机制涉及 2,4-二硝基苯基和甘氨酸亚甲基之间的初始光驱动环化，形成酰基苯并咪唑 N-氧化物，其经历二次光诱导脱羧与酰胺键断裂相关。裂解反应以适度到高的量子产率进行。我们证明这些衍生物可用于 Zn2+ 的靶向细胞内递送，通过光触发 Zn2+ 释放进行荧光成像，和调节生物过程，包括碳酸酐酶 (CA) 的酶活性、N-甲基-D-天冬氨酸受体 (NMDAR) 的负调节和心肌细胞的脉搏率。上述成功的概念验证示例为使用基于 Sanger 试剂的甘氨酸酰胺作为光笼探索复杂的细胞功能和信号通路开辟了一条新途径。

更新日期：2020-02-05

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