Expedient synthesis and luminescence sensing of the inositol pyrophosphate cellular messenger 5-PP-InsP 5 .
Megan L ShiptonFathima A JamionSimon WheelerAndrew M RileyFelix PlasserBarry V L PotterStephen J ButlerPublished in: Chemical science (2023)
Inositol pyrophosphates are important biomolecules associated with apoptosis, cell growth and kinase regulation, yet their exact biological roles are still emerging and probes do not exist for their selective detection. We report the first molecular probe for the selective and sensitive detection of the most abundant cellular inositol pyrophosphate 5-PP-InsP 5 , as well as an efficient new synthesis. The probe is based on a macrocyclic Eu(iii) complex bearing two quinoline arms providing a free coordination site at the Eu(iii) metal centre. Bidentate binding of the pyrophosphate group of 5-PP-InsP 5 to the Eu(iii) ion is proposed, supported by DFT calculations, giving rise to a selective enhancement in Eu(iii) emission intensity and lifetime. We demonstrate the use of time-resolved luminescence as a bioassay tool for monitoring enzymatic processes in which 5-PP-InsP 5 is consumed. Our probe offers a potential screening methodology to identify drug-like compounds that modulate the activity of enzymes of inositol pyrophosphate metabolism.
Keyphrases
- quantum dots
- sensitive detection
- living cells
- density functional theory
- loop mediated isothermal amplification
- oxidative stress
- molecular docking
- energy transfer
- small molecule
- molecular dynamics
- endoplasmic reticulum stress
- emergency department
- cell death
- fluorescent probe
- molecular dynamics simulations
- protein kinase
- binding protein
- real time pcr
- nitric oxide
- transcription factor
- climate change