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用于剖析肌醇焦磷酸生理学的使能技术

Enabling Technologies for the Dissection of Inositol Pyrophosphate Physiology.

作者信息

Saiardi Adolfo, Jessen Henning J, Fiedler Dorothea

机构信息

Laboratory for Molecular Cell Biology, University College London, London, UK.

Institute of Organic Chemistry, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.

出版信息

Methods Mol Biol. 2025;2972:1-18. doi: 10.1007/978-1-0716-4799-8_1.

DOI:10.1007/978-1-0716-4799-8_1
PMID:40879974
Abstract

The diverse chemical structures of inositol pyrophosphates attract growing interest toward this class of small molecule messengers. However, their highly charged nature, the lack of a chromophore or a fluorophore, their close structural relatedness, and the complexity of their metabolism pose serious challenges to inositol pyrophosphates studies. Here, we summarize how researchers have begun to overcome these challenges and how recent experimental advances are propelling inositol pyrophosphate research into the future.

摘要

肌醇焦磷酸多样的化学结构吸引了人们对这类小分子信使越来越浓厚的兴趣。然而,它们高度带电的性质、缺乏发色团或荧光团、结构上的紧密相关性以及代谢的复杂性给肌醇焦磷酸的研究带来了严峻挑战。在此,我们总结了研究人员是如何开始克服这些挑战的,以及近期的实验进展如何推动肌醇焦磷酸研究走向未来。

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本文引用的文献

1
Synthesis of a New Purine Analogue Class with Antifungal Activity and Improved Potency against Fungal IPK.具有抗真菌活性且对真菌IPK效力增强的新型嘌呤类似物类的合成。
ACS Infect Dis. 2025 Apr 11;11(4):940-953. doi: 10.1021/acsinfecdis.4c00975. Epub 2025 Mar 31.
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Structural basis of phosphate export by human XPR1.人类XPR1介导磷酸盐输出的结构基础
Nat Commun. 2025 Jan 15;16(1):683. doi: 10.1038/s41467-025-55995-8.
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Inhibiting IP6K1 confers atheroprotection by elevating circulating apolipoprotein A-I.抑制肌醇六磷酸激酶1通过提高循环载脂蛋白A-I赋予动脉粥样硬化保护作用。
Metabolism. 2025 Feb;163:156098. doi: 10.1016/j.metabol.2024.156098. Epub 2024 Dec 4.
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Structural basis for inositol pyrophosphate gating of the phosphate channel XPR1.肌醇焦磷酸门控磷酸通道 XPR1 的结构基础。
Science. 2024 Nov 15;386(6723):eadp3252. doi: 10.1126/science.adp3252.
5
The Ip6k1 and Ip6k2 Kinases Are Critical for Normal Renal Tubular Function.Ip6k1 和 Ip6k2 激酶对于正常的肾小管功能至关重要。
J Am Soc Nephrol. 2024 Apr 1;35(4):441-455. doi: 10.1681/ASN.0000000000000303. Epub 2024 Feb 6.
6
Depleting inositol pyrophosphate 5-InsP7 protected the heart against ischaemia-reperfusion injury by elevating plasma adiponectin.耗竭肌醇五磷酸 5-InsP7 通过提高血浆脂联素水平保护心脏免受缺血再灌注损伤。
Cardiovasc Res. 2024 Jul 2;120(8):954-970. doi: 10.1093/cvr/cvae017.
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Biochemical and structural characterization of an inositol pyrophosphate kinase from a giant virus.一种巨型病毒肌醇六磷酸激酶的生化和结构特征。
EMBO J. 2024 Feb;43(3):462-480. doi: 10.1038/s44318-023-00005-0. Epub 2024 Jan 12.
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Fragment-Based Screening Identifies New Quinazolinone-Based Inositol Hexakisphosphate Kinase (IP6K) Inhibitors.基于片段的筛选鉴定出新型喹唑啉酮类肌醇六磷酸激酶(IP6K)抑制剂。
ACS Med Chem Lett. 2023 Nov 28;14(12):1760-1766. doi: 10.1021/acsmedchemlett.3c00409. eCollection 2023 Dec 14.
9
Inositol hexakisphosphate kinase 1 is essential for cell junction integrity in the mouse seminiferous epithelium.肌醇六磷酸激酶 1 对于精子表皮细胞连接完整性至关重要。
Biochim Biophys Acta Mol Cell Res. 2024 Jan;1871(1):119596. doi: 10.1016/j.bbamcr.2023.119596. Epub 2023 Sep 22.
10
Capillary electrophoresis mass spectrometry identifies new isomers of inositol pyrophosphates in mammalian tissues.毛细管电泳质谱法鉴定哺乳动物组织中肌醇焦磷酸的新异构体。
Chem Sci. 2022 Dec 5;14(3):658-667. doi: 10.1039/d2sc05147h. eCollection 2023 Jan 18.