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

Autor: Shipton ML; Medicinal Chemistry & Drug Discovery, Department of Pharmacology, University of Oxford Mansfield Road Oxford OX1 3QT UK barry.potter@pharm.ox.ac.uk., Jamion FA; Department of Chemistry, Loughborough University Epinal Way, Loughborough LE11 3TU UK S.J.Butler@lboro.ac.uk., Wheeler S; Department of Chemistry, Loughborough University Epinal Way, Loughborough LE11 3TU UK S.J.Butler@lboro.ac.uk., Riley AM; Medicinal Chemistry & Drug Discovery, Department of Pharmacology, University of Oxford Mansfield Road Oxford OX1 3QT UK barry.potter@pharm.ox.ac.uk., Plasser F; Department of Chemistry, Loughborough University Epinal Way, Loughborough LE11 3TU UK S.J.Butler@lboro.ac.uk., Potter BVL; Medicinal Chemistry & Drug Discovery, Department of Pharmacology, University of Oxford Mansfield Road Oxford OX1 3QT UK barry.potter@pharm.ox.ac.uk., Butler SJ; Department of Chemistry, Loughborough University Epinal Way, Loughborough LE11 3TU UK S.J.Butler@lboro.ac.uk.
Jazyk: angličtina
Zdroj: Chemical science [Chem Sci] 2023 Apr 13; Vol. 14 (19), pp. 4979-4985. Date of Electronic Publication: 2023 Apr 13 (Print Publication: 2023).
DOI: 10.1039/d2sc06812e
Abstrakt: 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.
Competing Interests: There are no conflicts to declare.
(This journal is © The Royal Society of Chemistry.)
Databáze: MEDLINE
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