A Fluorescent Kinase Inhibitor that Exhibits Diagnostic Changes in Emission upon Binding.
Angew Chem Int Ed Engl
; 58(42): 15000-15004, 2019 10 14.
Article
in En
| MEDLINE
| ID: mdl-31411364
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 700â
nm.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
/
Protein Kinase Inhibitors
/
Fluorescent Dyes
/
2-Naphthylamine
Type of study:
Diagnostic_studies
Limits:
Humans
Language:
En
Journal:
Angew Chem Int Ed Engl
Year:
2019
Type:
Article
Affiliation country:
Sweden