Resolving Heparan Sulfate Oligosaccharide Positional Isomers Using Hydrophilic Interaction Liquid Chromatography-Cyclic Ion Mobility Mass Spectrometry.
Resolving Heparan Sulfate Oligosaccharide Positional Isomers Using Hydrophilic Interaction Liquid Chromatography-Cyclic Ion Mobility Mass Spectrometry.
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DOI：
10.1021/acs.analchem.1c03543
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发表时间：
2022-02-08
影响因子：
7.4
通讯作者：
Zaia J
中科院分区：
文献类型：
--
作者：
Cavallero GJ;Zaia J
硫酸乙酰肝素 (HS) 是一种线性多糖，共价附着在所有动物组织细胞表面和细胞外基质内的蛋白聚糖上。许多生物过程是由 HS 结合蛋白和 HS 链中的短结构基序之间的相互作用触发的。由于位置硫酸化和乙酰化异构体的存在，使用液相色谱-质谱 (LC-MS) 测定 HS 寡糖结构具有挑战性。糖醛酸差向异构体位置的确定更具挑战性。虽然亲水相互作用液相色谱 (HILIC) 根据 HS 糖的组成来分离它们，但位置异构体的分辨率非常有限。这种分辨率的缺乏给用于指定糖异构体的串联质谱步骤带来了负担。在这项工作中，我们探索了使用离子淌度维度根据气相中的分子形状分离 HS 糖异构体。我们表明，HILIC 和循环离子淌度质谱 (cIM-MS) 的结合对于解析 HS 位置异构体（包括糖醛酸差向异构体和硫酸盐位置）非常有用。此外，HILIC-cIM-MS 还可区分多组分 HS 异构糖混合物。总之，HILIC-cIM-MS 为 HS 寡糖异构体混合物的分析提供了高质量的数据，这可能有助于发现 HS 结合蛋白的新结构基序以及商业 HS 产品的靶向质量控制分析。
Heparan sulfate (HS) is a linear polysaccharide covalently attached to proteoglycans on cell surfaces and within extracellular matrices in all animal tissues. Many biological processes are triggered by the interactions among HS binding proteins and short structural motifs in HS chains. The determination of HS oligosaccharide structures using liquid chromatography-mass spectrometry (LC-MS) is made challenging by the existence of positional sulfation and acetylation isomers. The determination of uronic acid epimer positions is even more challenging. While hydrophilic interaction liquid chromatography (HILIC) separates HS saccharides based on their composition, there is a very limited resolution of positional isomers. This lack of resolution places a burden on the tandem mass spectrometry step for assigning saccharide isomers. In this work, we explored the use of the ion mobility dimension to separate HS saccharide isomers based on molecular shape in the gas phase. We showed that the combination of HILIC and cyclic ion mobility mass spectrometry (cIM-MS) was extremely useful for resolving HS positional isomers including uronic acid epimers and sulfate positions. Furthermore, HILIC-cIM-MS differentiated multicomponent HS isomeric saccharide mixtures. In summary, HILIC-cIM-MS provided high-quality data for analysis of HS oligosaccharide isomeric mixtures that may prove useful in the discovery of new structural motifs for HS binding proteins and for the targeted quality control analysis of commercial HS products.
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影响因子：
3.4
作者：
Staples, Gregory O.;Bowman, Michael J.;Costello, Catherine E.;Hitchcock, Alicia M.;Lau, James M.;Leymarie, Nancy;Miller, Christine;Naimy, Hicham;Shi, Xiaofeng;Zaia, Joseph
通讯作者：
Zaia, Joseph
DOI：
10.1074/mcp.r120.002267
发表时间：
2021
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Pepi LE;Sanderson P;Stickney M;Amster IJ
通讯作者：
Amster IJ
影响因子：
7
作者：
Hogan, John D.;Klein, Joshua A.;Zaia, Joseph
通讯作者：
Zaia, Joseph
影响因子：
7.4
作者：
Miller, Rebecca L.;Guimond, Scott E.;Karlsson, Niclas
通讯作者：
Karlsson, Niclas
影响因子：
15
作者：
Arungundram, Sailaja;Al-Mafraji, Kanar;Asong, Jinkeng;Leach, Franklin E., III;Amster, I. Jonathan;Venot, Andre;Turnbull, Jeremy E.;Boons, Geert-Jan
通讯作者：
Boons, Geert-Jan