A Fluorescent Kinase Inhibitor that Exhibits Diagnostic Changes in Emission upon Binding
Journal article, 2019

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.

kinase

solvatochromism

inhibitors

fluorescence

Author

Cassandra Fleming

University of Gothenburg

Patrick A. Sandoz

Royal Institute of Technology (KTH)

Tord Inghardt

AstraZeneca AB

B. Onfelt

Karolinska University Hospital

Royal Institute of Technology (KTH)

Morten Grötli

University of Gothenburg

Joakim Andreasson

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry

Angewandte Chemie - International Edition

1433-7851 (ISSN) 1521-3773 (eISSN)

Vol. 58 42 15000-15004

Subject Categories

Pharmaceutical Sciences

Atom and Molecular Physics and Optics

Medicinal Chemistry

DOI

10.1002/anie.201909536

PubMed

31411364

More information

Latest update

11/11/2019