Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Institute of Molecular Science , Shanxi University , Taiyuan 030006 , P. R. China.
Research Institute of Applied Chemistry , Shanxi University , Taiyuan 030006 , P. R. China.
Anal Chem. 2019 Feb 5;91(3):2255-2259. doi: 10.1021/acs.analchem.8b04836. Epub 2019 Jan 15.
Noradrenaline as one of the most important neurotransmitters in the sympathetic nervous system plays key roles in all of the forebrain activities such as perception, memory, learning, and homeostasis, and its dysfunction is closely related to both neurodegenerative diseases and central nervous system disorders. The very similar structures and properties of the three coexisting catecholamine neurotransmitters-dopamine, epinephrine, and noradrenaline-make it almost impossible to design fluorescent probes that respond specifically to noradrenaline, which restricted its physiological and pathological studies greatly. Fantastic design turned dreams into reality in this work: the cascade nucleophilic substitution reactions between noradrenaline and fluorophore coupling carbonic ester, which formed a five-membered ring catechol-containing compound with the release of the fluorophore accompanied by unique fluorescent responses, allowed us to develop a fluorescent probe to detect and visualize noradrenaline over dopamine and epinephrine in brain tissue. Instead of the noradrenaline synzyme immunofluorescence labeling path, the present fluorescent probe can visualize noradrenaline directly with comparable specificity.
去甲肾上腺素作为交感神经系统中最重要的神经递质之一，在大脑的所有活动中（如感知、记忆、学习和体内平衡）都起着关键作用，其功能障碍与神经退行性疾病和中枢神经系统疾病密切相关。三种共存的儿茶酚胺神经递质——多巴胺、肾上腺素和去甲肾上腺素——具有非常相似的结构和性质，这使得设计专门针对去甲肾上腺素的荧光探针几乎不可能，这极大地限制了其生理和病理研究。在这项工作中，奇妙的设计将梦想变为现实：去甲肾上腺素与荧光团偶联碳酸酯之间的级联亲核取代反应，形成一个含有五员环儿茶酚的化合物，伴随着荧光团的释放，同时伴随着独特的荧光响应，使我们能够开发一种荧光探针来检测和可视化脑组织中的去甲肾上腺素，而不是多巴胺和肾上腺素。与去甲肾上腺素的酶免疫荧光标记途径不同，这种荧光探针可以直接可视化去甲肾上腺素，具有可比的特异性。
