Elucidating diphosphoinositol polyphosphate function with nonhydrolyzable analogues.
Elucidating diphosphoinositol polyphosphate function with nonhydrolyzable analogues.
复制标题
用不可水解的类似物阐明二磷酸肌醇多磷酸的功能。
DOI：
10.1002/anie.201402905
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Fiedler,Dorothea
中科院分区：
文献类型：
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作者：
Wu,Mingxuan;Chong,LucyS;Capolicchio,Samanta;Jessen,HenningJ;Resnick,AdamC;Fiedler,Dorothea
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‐IP5and 5PCP‐IP5inhibited Akt phosphorylation with similar potencies, 1PCP‐IP5was much more effective at inhibiting its cognate phosphatase hDIPP1. Furthermore, the PCP analogues inhibit protein pyrophosphorylation because of their inability to transfer the β‐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.
