[en] A previously disclosed protein kinase (PK) CK2-selective inhibitor 4-(2-amino-1,3-thiazol-5-yl)benzoic acid (ATB) and its selenium-containing counterpart (ASB) revealed remarkable room temperature phosphorescence when bound to the ATP pocket of the protein kinase CK2. Conjugation of these fragments with a mimic of CK2 substrate peptide resulted in bisubstrate inhibitors with increased affinity towards the kinase. Attachment of the fluorescent acceptor dye 5-TAMRA to the conjugates led to significant enhancement of intensity of long-lifetime (microsecond-scale) photoluminescence of both sulfur- and selenium-containing compounds. The developed photoluminescent probes make possible selective determination of the concentration of CK2 in cell lysates and characterization of CK2 inhibitors by means of time-gated measurement of photoluminescence.
Disciplines :
Chemistry
Author, co-author :
Vahter, Jurgen; University of Tartu
Viht, Kaido; University of Tartu
Uri, Asko; University of Tartu
MANOHARAN, Ganesh Babu ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Enkvist, Erki; University of Tartu
External co-authors :
yes
Language :
English
Title :
Thiazole- and selenazole-comprising high-affinity inhibitors possess bright microsecond-scale photoluminescence in complex with protein kinase CK2.
Publication date :
2018
Journal title :
Bioorganic & medicinal chemistry
ISSN :
0968-0896
eISSN :
1464-3391
Volume :
26
Issue :
18
Pages :
5062-5068
Peer reviewed :
Peer reviewed
Commentary :
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