Thiazole- and selenazole-comprising high-affinity inhibitors possess bright microsecond-scale photoluminescence in complex with protein kinase CK2

Bioorg Med Chem. 2018 Oct 1;26(18):5062-5068. doi: 10.1016/j.bmc.2018.09.003. Epub 2018 Sep 5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Casein Kinase II / antagonists & inhibitors
  • Casein Kinase II / metabolism
  • Dose-Response Relationship, Drug
  • Fluorescence
  • Fluorescence Polarization
  • Fluorescent Dyes / chemistry*
  • Humans
  • Molecular Structure
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / pharmacology*
  • Photochemical Processes
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*
  • Time Factors

Substances

  • Fluorescent Dyes
  • Organoselenium Compounds
  • Protein Kinase Inhibitors
  • Thiazoles
  • CSNK2A1 protein, human
  • Casein Kinase II