Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 53, Issue 28, Pages 7192-7197Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201402905
Keywords
diphosphoinositol polyphosphate; mechanistic probe; nonhydrolyzable analogues; second messengers; phosphorylation
Categories
Funding
- Princeton University
- NIH [R00 GM087306]
- NSF [MCB-1253809]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1253809] Funding Source: National Science Foundation
Ask authors/readers for more resources
The diphosphoinositol polyphosphates (PP-IPs) represent a novel class of high-energy phosphate-containing messengers which control a wide variety of cellular processes. It is thought that PP-IPs exert their pleiotropic effects as allosteric regulators and through pyrophosphorylation of protein substrates. However, most details of PP-IP signaling have remained elusive because of a paucity of suitable tools. We describe the synthesis of PP-IP bisphosphonate analogues (PCP-IPs), which are resistant to chemical and biochemical degradation. While the two regioisomers 1PCP-IP5 and 5PCP-IP5 inhibited Akt phosphorylation with similar potencies, 1PCP-IP5 was much more effective at inhibiting its cognate phosphatase hDIPP1. Furthermore, the PCP analogues inhibit protein pyrophosphorylation because of their inability to transfer the beta-phosphoryl group, and thus enable the distinction between PP-IP signaling mechanisms. As such, the PCP analogues will find widespread applications for the structural and biochemical characterization of PP-IP signaling properties.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available