Kinase-templated abiotic reaction. Issue 7 (30th May 2017)

• Record Type: Journal Article
• Authors: Saarbach, J.; Lindberg, E.; Folliet, S.; Georgeon, S.; Hantschel, O.; Winssinger, N.
• Is Part Of: Chemical science. Volume 8:Issue 7(2017)
• Page Start: 5119
• Page End: 5125
• Publication Date: 2017-05-30
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c7sc01416c
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Protein kinases are quintessential regulators of cellular function. 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.