期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 142, 期 49, 页码 20701-20707出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.0c09200
关键词
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资金
- MEXT/JSPS KAKENHI [JP15H05951, JP19H02826, JP19K22242, JP20H05723, JP20H05724]
- JSPS KAKENHI [JP20H02650, JP20H05725, JP19J22546]
- JSPS Core-to-Core Program [JPJSCCA20170007]
- JST CREST [JPMJCR1872]
- Japan Foundation for Applied Enzymology
- Naito Foundation
- Quantum Leap Flagship Program of MEXT [JPMXS0118067246]
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.
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