A Fluorescent Kinase Inhibitor that Exhibits Diagnostic Changes in Emission upon Binding
Artikel i vetenskaplig tidskrift, 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.

solvatochromism

kinase

fluorescence

inhibitors

Författare

Cassandra Fleming

Göteborgs universitet

Patrick A. Sandoz

Kungliga Tekniska Högskolan (KTH)

Tord Inghardt

AstraZeneca AB

B. Onfelt

Karolinska universitetssjukhuset

Kungliga Tekniska Högskolan (KTH)

Morten Grötli

Göteborgs universitet

Joakim Andreasson

Chalmers, Kemi och kemiteknik, Kemi och biokemi

Angewandte Chemie - International Edition

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

Vol. 58 42 15000-15004

Styrkeområden

Nanovetenskap och nanoteknik (SO 2010-2017, EI 2018-)

Ämneskategorier

Farmaceutisk vetenskap

Atom- och molekylfysik och optik

Läkemedelskemi

DOI

10.1002/anie.201909536

PubMed

31411364

Mer information

Senast uppdaterat

2020-08-31