具有增强动态范围的锌敏传感器，用于成像神经元细胞对锌的摄取和动员。
Zinspy sensors with enhanced dynamic range for imaging neuronal cell zinc uptake and mobilization.
作者信息
Nolan Elizabeth M, Ryu Jubin W, Jaworski Jacek, Feazell Rodney P, Sheng Morgan, Lippard Stephen J
机构信息
Department of Chemistry, Picower Institute of Learning and Memory, RIKEN-MIT Neuroscience Research Center, and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
出版信息
J Am Chem Soc. 2006 Dec 6;128(48):15517-28. doi: 10.1021/ja065759a.
Thiophene moieties were incorporated into previously described Zinspy (ZS) fluorescent Zn(II) sensor motifs (Nolan, E. M.; Lippard, S. J. Inorg. Chem. 2004, 43, 8310-8317) to provide enhanced fluorescence properties, low-micromolar dissociation constants for Zn(II), and improved Zn(II) selectivity. Halogenation of the xanthenone and benzoate moieties of the fluorescein platform systematically modulates the excitation and emission profiles, pH-dependent fluorescence, Zn(II) affinity, and Zn(II) complexation rates, offering a general strategy for tuning multiple properties of xanthenone-based metal ion sensors. Extensive biological studies in cultured cells and primary neuronal cultures demonstrate 2-{6-hydroxy-3-oxo-4,5-bis[(pyridin-2-ylmethylthiophen-2-ylmethylamino)methyl]-3H-xanthen-9-yl}benzoic acid (ZS5) to be a versatile imaging tool for detecting Zn(II) in vivo. ZS5 localizes to the mitochondria of HeLa cells and allows visualization of glutamate-mediated Zn(II) uptake in dendrites and Zn(II) release resulting from nitrosative stress in neurons.
噻吩部分被引入到先前描述的Zinspy（ZS）荧光锌（II）传感器基序中（诺兰，E.M.；利帕德，S.J.《无机化学》2004年，43卷，8310 - 8317页），以提供增强的荧光特性、低微摩尔级的锌（II）解离常数以及改善的锌（II）选择性。荧光素平台的呫吨酮和苯甲酸酯部分的卤化系统地调节激发和发射光谱、pH依赖性荧光、锌（II）亲和力以及锌（II）络合速率，为调节基于呫吨酮的金属离子传感器的多种性质提供了一种通用策略。在培养细胞和原代神经元培养物中的广泛生物学研究表明，2 - {6 - 羟基 - 3 - 氧代 - 4,5 - 双[（吡啶 - 2 - 基甲基噻吩 - 2 - 基甲基氨基）甲基] - 3H - 呫吨 - 9 - 基}苯甲酸（ZS5）是一种用于体内检测锌（II）的通用成像工具。ZS5定位于HeLa细胞的线粒体，并允许可视化谷氨酸介导的锌（II）在树突中的摄取以及神经元中亚硝化应激导致的锌（II）释放。
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