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Issue 1, 2013
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Synthesis and characterization of non-hydrolysable diphosphoinositol polyphosphate messengers

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Abstract

The diphosphoinositol polyphosphates (PP-IPs) are a central group of eukaryotic 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.

Graphical abstract: Synthesis and characterization of non-hydrolysable diphosphoinositol polyphosphate messengers

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Publication details

The article was received on 19 Sep 2012, accepted on 04 Oct 2012 and first published on 08 Oct 2012


Article type: Edge Article
DOI: 10.1039/C2SC21553E
Chem. Sci., 2013,4, 405-410

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    Synthesis and characterization of non-hydrolysable diphosphoinositol polyphosphate messengers

    M. Wu, B. E. Dul, A. J. Trevisan and D. Fiedler, Chem. Sci., 2013, 4, 405
    DOI: 10.1039/C2SC21553E

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