Multicolor Activatable Raman Probes for Simultaneous Detection of Plural Enzyme Activities
Multicolor Activatable Raman Probes for Simultaneous Detection of Plural Enzyme Activities
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DOI：
10.1021/jacs.0c09200
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发表时间：
2020-12-09
影响因子：
15
通讯作者：
Kamiya, Mako
中科院分区：
文献类型：
--
作者：
Fujioka, Hiroyoshi;Shou, Jingwen;Kamiya, Mako
基于炔或亚硝酸盐标签的拉曼探针有望用于高度多重成像。然而，用拉曼探针检测酶活性是困难的，因为很少有机制可用于调节振动响应。在这里，我们提出了一个一般的策略，以制备可激活的拉曼探针，显示增强的拉曼信号，由于电子预共振（EPR）在生理条件下与酶反应。我们确定了一种在9位带有腈基的咕吨衍生物（9 CN-JCP）作为合适的支架染料，并合成了四种类型的可活化拉曼探针，它们针对不同的酶（三种氨肽酶和一种糖苷酶），并通过腈基的同位素编辑调谐到不同的振动频率。我们验证了这些探针的拉曼信号被靶酶激活，并成功地在活细胞中同时成像四种酶的活性。不同的细胞系表现出不同的模式，这些酶的活动。
Raman probes based on alkyne or nitrite tags hold promise for highly multiplexed imaging. However, sensing of enzyme activities with Raman probes is difficult because few mechanisms are available to modulate the vibrational response. Here we present a general strategy to prepare activatable Raman probes that show enhanced Raman signals due to electronic preresonance (EPR) upon reaction with enzymes under physiological conditions. We identified a xanthene derivative bearing a nitrile group at position 9 (9CN-JCP) as a suitable scaffold dye, and synthesized four types of activatable Raman probes, which are targeted to different enzymes (three aminopeptidases and a glycosidase) and tuned to different vibrational frequencies by isotope editing of the nitrile group. We validated the activation of the Raman signals of these probes by the target enzymes and succeeded in simultaneous imaging of the four enzyme activities in live cells. Different cell lines showed different patterns of these enzyme activities.