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A Fluorescent Kinase Inhibitor that Exhibits Diagnostic Changes in Emission upon Binding
Author(s) -
Fleming Cassandra L.,
Sandoz Patrick A.,
Inghardt Tord,
Önfelt Björn,
Grøtli Morten,
Andréasson Joakim
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201909536
Subject(s) - fluorophore , fluorescence , solvatochromism , hypsochromic shift , biophysics , chemistry , biology , optics , physics
Abstract 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.