A Fluorescent Kinase Inhibitor that Exhibits Diagnostic Changes in Emission upon Binding.

Fleming CL, Sandoz PA, Inghardt T, Önfelt B, Grøtli M, Andréasson J

Angew. Chem. Int. Ed. Engl. 58 (42) 15000-15004 [2019-10-14; online 2019-09-05]

The development of a fluorescent LCK inhibitor that exhibits favourable solvatochromic properties upon binding the kinase is described. Fluorescent properties were realised through the inclusion of a prodan-derived fluorophore into the pharmacophore of an ATP-competitive kinase inhibitor. Fluorescence titration experiments demonstrate the solvatochromic properties of the inhibitor, in which dramatic increase in emission intensity and hypsochromic shift in emission maxima are clearly observed upon binding LCK. Microscopy experiments in cellular contexts together with flow cytometry show that the fluorescence intensity of the inhibitor correlates with the LCK concentration. Furthermore, multiphoton microscopy experiments demonstrate both the rapid cellular uptake of the inhibitor and that the two-photon cross section of the inhibitor is amenable for excitation at 700 nm.

Integrated Microscopy Technologies Gothenburg [Service]

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PubMed 31411364

DOI 10.1002/anie.201909536

Crossref 10.1002/anie.201909536

pmc: PMC6851755