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用于成像溶酶体锌离子的比率型和靶向荧光探针的合理设计。

Rational design of a ratiometric and targetable fluorescent probe for imaging lysosomal zinc ions.

机构信息

Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 PR China.

出版信息

Inorg Chem. 2012 Oct 15;51(20):10842-9. doi: 10.1021/ic301307v. Epub 2012 Sep 27.

DOI:10.1021/ic301307v
PMID:23016704
Abstract

Fluorescent detecting and tracking of zinc ions in living cells has become more and more important because the physiological and pathological functions of zinc are highly associated with the timing and discrete distribution of subcellular zinc ion. For the detection of subcellular zinc concentrations with high spatial and temporal reliability, we report the design, synthesis, properties, and bioimaging evaluation of a fluorescent probe, DQZn4, composed of a quinoline scaffold as the ratiometric signaling unit for Zn(2+) and a dimethylethylamino group as the targeting anchor for lysosomes. In acidic aqueous solution (pH = 5.2), DQZn4 features fluorescence emission maximum at 542 nm due to the resonance charge transfer in 4-alkoxy substituted quinoline. Upon binding Zn(2+), the probe displays significant fluorescent turn-on and ratiometric detection of Zn(2+) with blue shift of 47 nm and remarkable fluorescence ratio changes (R = F(495)/F(542 nm), R/R(0) = 5.1). Confocal imaging experiments establish that DQZn4 is able to localize to lysosomes and respond to lysosomal zinc changes in living cells by using fluorescence ratiometry.

摘要

荧光检测和跟踪活细胞中的锌离子变得越来越重要,因为锌的生理和病理功能与亚细胞锌离子的时间和离散分布密切相关。为了以高时空可靠性检测亚细胞锌浓度,我们报告了荧光探针 DQZn4 的设计、合成、性质和生物成像评价,它由喹啉支架组成,作为 Zn(2+) 的比率信号单元,二甲乙基氨基作为溶酶体的靶向锚。在酸性水溶液(pH = 5.2)中,由于 4-烷氧基取代喹啉中的共振电荷转移,DQZn4 在 542nm 处具有荧光发射最大值。与 Zn(2+)结合后,探针显示出显著的荧光开启和 Zn(2+)的比率检测,蓝移 47nm,荧光比变化显著(R = F(495)/F(542nm),R/R(0) = 5.1)。共聚焦成像实验表明,DQZn4 能够定位于溶酶体,并通过荧光比率法响应活细胞中溶酶体锌的变化。

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