Hunan Provincial Key Laboratory of Cytochemistry, School of Chemistry and Food Engineering, Changsha University of Science and Technology, Changsha 410114, P.R. China.
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410003, P.R. China.
Anal Chem. 2020 May 19;92(10):7194-7199. doi: 10.1021/acs.analchem.0c00746. Epub 2020 Apr 30.
Tyrosinase (TYR) is a crucial enzyme involved in melanogenesis, and its overexpression is closely associated with melanoma. To precisely monitor intracellular TYR activity, remote control of a molecule imaging tool is highly meaningful but remains to be explored. In this work, we present the first photocaged tyrosinase fluorogenic probe by caging the substrate of the enzymatic probe with a photolabile group. Because of the sequential light and enzyme-activation feature, this probe exhibits photocontrollable "turn on" response toward TYR with good selectivity and high sensitivity (detection limit: 0.08 U/mL). Fluorescence imaging results validate that the caged probe possesses the capability of visualizing intracellular endogenous tyrosinase activity in a photocontrol fashion, thus offering a promising molecule imaging tool for investigating TYR-related physiological function and pathological role. Moreover, our sequential activation strategy has great potential for developing more photocontrollable enzymatic fluorogenic probes with spatiotemporal resolution.
酪氨酸酶（TYR）是参与黑色素生成的关键酶，其过度表达与黑色素瘤密切相关。为了精确监测细胞内 TYR 的活性，对分子成像工具进行远程控制具有重要意义，但这方面的研究仍有待探索。在这项工作中，我们通过用光不稳定基团对酶探针的底物进行笼蔽，首次开发了一种光笼酪氨酸酶荧光探针。由于具有顺序光和酶激活的特点，该探针对 TYR 表现出光可控的“开启”响应，具有良好的选择性和高灵敏度（检测限：0.08 U/mL）。荧光成像结果验证了该笼蔽探针具有以光控方式可视化细胞内内源性酪氨酸酶活性的能力，从而为研究 TYR 相关生理功能和病理作用提供了一种有前途的分子成像工具。此外，我们的顺序激活策略为开发具有时空分辨率的更多光可控酶荧光探针提供了巨大潜力。
