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Kinase-templated abiotic reaction

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Abstract

Protein kinases are quintessential regulators of cellular function. Numerous pathologies are intimately linked to the dysregulated activity of a particular protein kinase. Herein we report a technology based on a proximity-induced chemical transformation that enables the detection and imaging of specific kinases. Using two probes that target the nucleotide-binding site and substrate binding site of a target kinase respectively, the reagents appended on the probes are brought within reactive distance thereby enabling the chemical transformation. The reaction used for sensing is a ruthenium-photocatalyzed reduction of a pyridinium immolative linker, which uncages a fluorophore (rhodamine). We demonstrate that this technology can be used to discriminate between closely related kinases with a high signal to noise ratio. We further demonstrate that the technology operates within the complexity of a cellular context with a good correlation between the level of kinase activity and fluorescence output.

Graphical abstract: Kinase-templated abiotic reaction

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Publication details

The article was received on 30 Mar 2017, accepted on 20 May 2017 and first published on 24 May 2017


Article type: Edge Article
DOI: 10.1039/C7SC01416C
Citation: Chem. Sci., 2017, Advance Article
  • Open access: Creative Commons BY-NC license
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    Kinase-templated abiotic reaction

    J. Saarbach, E. Lindberg, S. Folliet, S. Georgeon, O. Hantschel and N. Winssinger, Chem. Sci., 2017, Advance Article , DOI: 10.1039/C7SC01416C

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