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通过核磁共振光谱法确定的肌醇多磷酸酯和焦磷酸酯的绝对构型

Absolute Configurations of Inositol Poly- and Pyrophosphates Assigned by Nuclear Magnetic Resonance Spectroscopy.

作者信息

Ritter Kevin, Jessen Henning J

机构信息

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

出版信息

Methods Mol Biol. 2025;2972:115-123. doi: 10.1007/978-1-0716-4799-8_9.

DOI:10.1007/978-1-0716-4799-8_9
PMID:40879982
Abstract

Inositol phosphates are signaling molecules crucial for cellular processes. To achieve specificity, their diverse phosphorylation patterns necessitate precise molecular identification. Phosphorylation of the myo-inositol scaffold can form enantiomeric pairs, but most analysis methods only resolve regioisomers. This chapter presents an approach for enantiomer assignment using P-NMR with L-arginine amide as a chiral solvating agent. Chemically synthesized standards enabled clear enantiomer differentiation. This method applies to both inositol phosphates as well as inositol pyrophosphates and their bisphosphonate analogs, aiding in the identification of biologically relevant isomers in natural samples.

摘要

肌醇磷酸是细胞过程中至关重要的信号分子。为实现特异性,其多样的磷酸化模式需要精确的分子鉴定。肌醇骨架的磷酸化可形成对映体对,但大多数分析方法只能分辨区域异构体。本章介绍了一种使用L-精氨酸酰胺作为手性溶剂化剂的磷核磁共振(P-NMR)对映体归属方法。化学合成标准品能够实现清晰的对映体区分。该方法适用于肌醇磷酸以及肌醇焦磷酸及其双膦酸盐类似物,有助于鉴定天然样品中具有生物学相关性的异构体。

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本文引用的文献

1
β-lapachone regulates mammalian inositol pyrophosphate levels in an NQO1- and oxygen-dependent manner.β-拉帕醌以 NQO1 和氧依赖的方式调节哺乳动物肌醇焦磷酸水平。
Proc Natl Acad Sci U S A. 2023 Aug 22;120(34):e2306868120. doi: 10.1073/pnas.2306868120. Epub 2023 Aug 14.
2
Assigning the Absolute Configuration of Inositol Poly- and Pyrophosphates by NMR Using a Single Chiral Solvating Agent.利用手性溶剂通过 NMR 对肌醇多聚和焦磷酸盐的绝对构型进行赋值。
Biomolecules. 2023 Jul 19;13(7):1150. doi: 10.3390/biom13071150.
3
The phytase RipBL1 enables the assignment of a specific inositol phosphate isomer as a structural component of human kidney stones.
植酸酶RipBL1能够确定一种特定的肌醇磷酸异构体作为人类肾结石的结构成分。
RSC Chem Biol. 2023 Jan 27;4(4):300-309. doi: 10.1039/d2cb00235c. eCollection 2023 Apr 5.
4
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.
5
Inositol pyrophosphate profiling reveals regulatory roles of IP6K2-dependent enhanced IP metabolism in the enteric nervous system.肌醇六磷酸激酶 2 依赖性增强的肌醇六磷酸代谢在肠神经系统中的调控作用的焦磷酸肌醇谱分析。
J Biol Chem. 2023 Mar;299(3):102928. doi: 10.1016/j.jbc.2023.102928. Epub 2023 Jan 19.
6
Stable Isotopomers of Inositol Uncover a Complex MINPP1-Dependent Inositol Phosphate Network.肌醇的稳定同位素异构体揭示了一个复杂的依赖MINPP1的肌醇磷酸网络。
ACS Cent Sci. 2022 Dec 28;8(12):1683-1694. doi: 10.1021/acscentsci.2c01032. Epub 2022 Dec 5.
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Analysis of inositol phosphate metabolism by capillary electrophoresis electrospray ionization mass spectrometry.采用毛细管电泳-电喷雾电离质谱法分析肌醇磷酸盐代谢。
Nat Commun. 2020 Nov 27;11(1):6035. doi: 10.1038/s41467-020-19928-x.
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Chem Sci. 2019 Jan 10;10(9):2687-2692. doi: 10.1039/c8sc03479f. eCollection 2019 Mar 7.