Synthesis and characterization of non-hydrolysable diphosphoinositol polyphosphate second messengers

The diphosphoinositol polyphosphates (PP-IPs) are a central group of eukaryotic second messengers. They regulate numerous processes, including cellular energy homeostasis and adaptation to environmental stresses. To date, most of the molecular details in PP-IP signalling have remained elusive, due t...

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Published inChemical science (Cambridge) Vol. 4; no. 1; pp. 405 - 410
Main Authors Wu, Mingxuan, Dul, Barbara E, Trevisan, Alexandra J, Fiedler, Dorothea
Format Journal Article
LanguageEnglish
Published England 01.01.2013
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Summary:The diphosphoinositol polyphosphates (PP-IPs) are a central group of eukaryotic second messengers. They regulate numerous processes, including cellular energy homeostasis and adaptation to environmental stresses. To date, most of the molecular details in PP-IP signalling have remained elusive, due to a lack of appropriate methods and reagents. Here we describe the expedient synthesis of methylene-bisphosphonate PP-IP analogues. Their characterization revealed that the analogues exhibit significant stability and mimic their natural counterparts very well. This was further confirmed in two independent biochemical assays, in which our analogues potently inhibited phosphorylation of the protein kinase Akt and hydrolytic activity of the Ddp1 phosphohydrolase. The non-hydrolysable PP-IPs thus emerge as important tools and hold great promise for a variety of applications.
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These authors contributed equally to this work.
ISSN:2041-6520
2041-6539
DOI:10.1039/C2SC21553E