Issue 19, 2023

Expedient synthesis and luminescence sensing of the inositol pyrophosphate cellular messenger 5-PP-InsP5

Abstract

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-InsP5, 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-InsP5 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-InsP5 is consumed. Our probe offers a potential screening methodology to identify drug-like compounds that modulate the activity of enzymes of inositol pyrophosphate metabolism.

Graphical abstract: Expedient synthesis and luminescence sensing of the inositol pyrophosphate cellular messenger 5-PP-InsP5

Supplementary files

Article information

Article type
Edge Article
Submitted
12 Dec. 2022
Accepted
07 Apr. 2023
First published
13 Apr. 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2023,14, 4979-4985

Expedient synthesis and luminescence sensing of the inositol pyrophosphate cellular messenger 5-PP-InsP5

M. L. Shipton, F. A. Jamion, S. Wheeler, A. M. Riley, F. Plasser, B. V. L. Potter and S. J. Butler, Chem. Sci., 2023, 14, 4979 DOI: 10.1039/D2SC06812E

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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