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A Fluorescent Kinase Inhibitor that Exhibits Diagnostic Changes in Emission upon Binding
Chalmers Univ Technol, Dept Chem & Chem Engn Phys Chem, S-41296 Gothenburg, Sweden.;Univ Gothenburg, Dept Chem & Mol Biol, S-41296 Gothenburg, Sweden..ORCID-id: 0000-0002-7730-7305
KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biofysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
AstraZeneca, Med Chem, Res & Early Dev Cardiovasc Renal & Metab, BioPharmaceut R&D, Gothenburg, Sweden..
KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biomedicinsk fysik och röntgenfysik.ORCID-id: 0000-0001-5178-7593
Vise andre og tillknytning
2019 (engelsk)Inngår i: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
WILEY-V C H VERLAG GMBH , 2019.
Emneord [en]
fluorescence, inhibitors, kinase, solvatochromism
HSV kategori
Identifikatorer
URN: urn:nbn:se:kth:diva-261016DOI: 10.1002/anie.201909536ISI: 000485136100001PubMedID: 31411364OAI: oai:DiVA.org:kth-261016DiVA, id: diva2:1356930
Merknad

QC 20191002

Tilgjengelig fra: 2019-10-02 Laget: 2019-10-02 Sist oppdatert: 2019-10-02bibliografisk kontrollert

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Fleming, Cassandra L.Sandoz, Patrick A.Önfelt, BjörnGrotli, MortenAndreasson, Joakim
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