期刊
ANALYTICAL CHEMISTRY
卷 84, 期 10, 页码 4404-4410出版社
AMER CHEMICAL SOC
DOI: 10.1021/ac300061a
关键词
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资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [22000006, 23651231]
- New Energy and Industrial Technology Development Organization (NEDO) of Japan
- Cosmetology Research Foundation
- Inoue Foundation for Science
- Konica Minolta Science and Technology Foundation
- Asahi Glass Foundation
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [23651231, 22000006] Funding Source: KAKEN
We present a novel design strategy for near-infrared (NIR) fluorescence probes utilizing dye-protein interaction as a trigger for fluorescence enhancement. The design principle involves modification of a polymethine dye with cleavable functional groups that reduce the dye's protein-binding affinity. When these functional groups are removed by specific interaction with the target enzymes, the dye's protein affinity is restored, protein binding occurs, and the dye's fluorescence is strongly enhanced. To validate this strategy, we first designed and synthesized an alkaline phosphatase (ALP) sensor by introducing phosphate into the squarylium dye scaffold; this sensor was able to detect ALP-labeled secondary antibodies in Western blotting analysis. Second, we synthesized a probe for beta-galactosidase (widely used as a reporter of gene expression) by means of beta-galactosyl substitution of the squarylium scaffold; this sensor was able to visualize beta-galactosidase activity both in vitro and in vivo. Our strategy should be applicable to obtain NIR fluorescence probes for a wide range of target enzymes.
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