Sensitive fluorescent biosensor based on a europium-based metal-organic framework for protein kinase activity analysis

Biosens Bioelectron. 2022 May 1:203:114055. doi: 10.1016/j.bios.2022.114055. Epub 2022 Feb 1.

Abstract

Protein kinases play crucial regulatory roles in the physiological activities in the human body. Understanding protein kinase activity and its inhibition is essential for the management of human diseases. Considering the limitations of the existing protein kinase-related analysis methods, the aim of the present study was to develop a fluorescent biosensor based on Eu(BTC) (H2O)6 (BTC = 1,3,5-Benzenetricarboxylic acid) for evaluating protein kinase activity and the relevant inhibitors. A fluorophore-labelled substrate polypeptide was phosphorylated under the catalysis of protein kinase. This phosphorylated peptide can be coordinated explicitly with the europium site of Eu(BTC) (H2O)6 to detect the protein kinase. The developed biosensor performed well, with a detection limit of 0.00003 U μL-1, and it showed good selectivity and universality. Protein kinase activity could also be detected in MCF-7 cells using this method. Furthermore, in terms of inhibitor screening using the Eu(BTC) (H2O)6-based sensor, both H-89 and ellagic acid were found to inhibit protein kinase activity with IC50 values of 1.09 and 19.88 nmol L-1, respectively. Overall, this biosensor has broad application prospects in monitoring and controlling protein kinase activity.

Keywords: Eu(BTC) (H(2)O)(6); Fluorescence; Inhibitor; Phosphorylation; Protein kinase activity.

MeSH terms

  • Biosensing Techniques* / methods
  • Europium
  • Metal-Organic Frameworks*
  • Phosphorylation
  • Protein Kinases / metabolism

Substances

  • Metal-Organic Frameworks
  • Europium
  • Protein Kinases