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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.

SUBMITTER: Shipton ML 

PROVIDER: S-EPMC10189900 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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

Shipton Megan L ML   Jamion Fathima A FA   Wheeler Simon S   Riley Andrew M AM   Plasser Felix F   Potter Barry V L BVL   Butler Stephen J SJ  

Chemical science 20230413 19

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<sub>5</sub>, as well as an efficient new synthesis. The probe is based on a macrocyclic Eu(iii) complex bearing two quinoline arms providin  ...[more]

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