Issue 1, 2013

Synthesis and characterization of non-hydrolysable diphosphoinositol polyphosphate messengers

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

Supplementary files

Article information

Article type
Edge Article
Submitted
19 Sep 2012
Accepted
04 Oct 2012
First published
08 Oct 2012

Chem. Sci., 2013,4, 405-410

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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