Turn-On Near-Infrared Fluorescent Sensor for Selectively Imaging Serotonin
Turn-On Near-Infrared Fluorescent Sensor for Selectively Imaging Serotonin
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DOI：
10.1021/acschemneuro.5b00235
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发表时间：
2016-01-01
影响因子：
5
通讯作者：
Glass, Timothy E.
中科院分区：
文献类型：
--
作者：
Hettie, Kenneth S.;Glass, Timothy E.
一种分子成像工具提供了血清素的直接可视化，将极大地帮助研究神经精神疾病，这些疾病归因于其神经元失调。本文介绍了神经传感器715 （NS715）的设计、合成和评价。NS715是第一个对血清素表现出近红外荧光反应的分子传感器。密度泛函理论计算促进了基于香豆素-3-醛支架的荧光团的设计，该支架来源于富电子的1,2,3,4-四氢喹啉框架，它提供了适当的能量来防止羟吲哚部分的5 -羟色胺猝灭其荧光发射。光谱研究表明，NS715对血清素产生8倍的荧光增强，在715 nm处发射最大值。伴随的结合研究表明，NS715对5 -羟色胺具有19倍的选择性亲和力，对儿茶酚胺的亲和力较其他初级胺类神经递质温和。NS715在神经成像方面的应用是通过使用活染色质细胞选择性标记和直接成像分泌囊泡内的去甲肾上腺素来验证的，活染色质细胞是专门神经元合成、包装和释放单一、独特类型的神经递质的模型系统。此外，NS715在表达不同神经递质表型的细胞群之间有效分化。
A molecular imaging tool that provides for the direct visualization of serotonin would significantly aid in the investigation of neuropsychiatric disorders that are attributed to its neuronal dysregulation. Here, the design, synthesis, and evaluation of NeuroSensor 715 (NS715) is presented. NS715 is the first molecular sensor that exhibits a turn-on near-infrared fluorescence response toward serotonin. Density functional theory calculations facilitated the design of a fluorophore based on a coumarin-3-aldehyde scaffold that derives from an electron-rich 1,2,3,4-tetrahydroquinoxaline framework, which provides appropriate energetics to prevent the hydroxyindole moiety of serotonin from quenching its fluorescence emission. Spectroscopic studies revealed that NS715 produces an 8-fold fluorescence enhancement toward serotonin with an emission maximum at 715 nm. Accompanying binding studies indicated NS715 displays a 19-fold selective affinity for serotonin and a modest affinity for catecholamines over other primary-amine neurotransmitters. The utility of NS715 toward neuroimaging applications was validated by selectively labeling and directly imaging norepinephrine within secretory vesicles using live chromaffin cells, which serve as a model system for specialized neurons that synthesize, package, and release only a single, unique type of neurotransmitter. In addition, NS715 effectively differentiated between cell populations that express distinct neurotransmitter phenotypes.