Electron detachment dissociation of synthetic heparan sulfate glycosaminoglycan tetrasaccharides varying in degree of sulfation and hexuronic acid stereochemistry
Electron detachment dissociation of synthetic heparan sulfate glycosaminoglycan tetrasaccharides varying in degree of sulfation and hexuronic acid stereochemistry
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DOI：
10.1016/j.ijms.2012.07.002
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发表时间：
2012-12-15
影响因子：
1.8
通讯作者：
Amster, I. Jonathan
中科院分区：
文献类型：
--
作者：
Leach, Franklin E.;Arungundram, Sailaja;Amster, I. Jonathan
糖胺聚糖 (GAG) 碳水化合物由于其多分散性、非模板生物合成和不稳定的硫酸盐修饰，为结构测定提供了具有挑战性的分析目标。所得结构虽然异质，但包含指示与特定功能相关的硫酸化模式或代码的域。质谱分析，特别是电子脱离解离傅立叶变换离子回旋共振 (EDD MICR MS)，通过提供硫酸化位置的跨环裂解和己糖醛酸立体化学特有的产物离子，为 GAG 结构分析提供了高度灵敏的平台。为了研究硫酸化模式和立体化学变化对 EDD 光谱的影响，检查了一系列合成的硫酸乙酰肝素 (HS) 四糖。之前的研究主要集中在低硫酸化化合物（每个二糖 0.5-1 个硫酸基团）上，而当前的工作将 EDD 的应用扩展到更高硫酸化的四糖（每个二糖 1-2 个硫酸基团），并首次提出了含有硫酸化己糖醛酸的四糖的 EDD。对于这些高度硫酸化的 HS 低聚物，替代策略被证明可以有效提取完整的结构细节。这些策略包括钠阳离子取代质子以确定硫酸化位点，以及寡糖脱硫以产生产物离子以指定糖醛酸立体化学。 (C) 2012 Elsevier B.V. 保留所有权利。
Glycosaminoglycan (GAG) carbohydrates provide a challenging analytical target for structural determination due to their polydisperse nature, non-template biosynthesis, and labile sulfate modifications. The resultant structures, although heterogeneous, contain domains which indicate a sulfation pattern or code that correlates to specific function. Mass spectrometry, in particular electron detachment dissociation Fourier transform ion cyclotron resonance (EDD MICR MS), provides a highly sensitive platform for GAG structural analysis by providing cross-ring cleavages for sulfation location and product ions specific to hexuronic acid stereochemistry. To investigate the effect of sulfation pattern and variations in stereochemistry on EDD spectra, a series of synthetic heparan sulfate (HS) tetrasaccharides are examined. Whereas previous studies have focused on lowly sulfated compounds (0.5-1 sulfate groups per disaccharide), the current work extends the application of EDD to more highly sulfated tetrasaccharides (1-2 sulfate groups per disaccharide) and presents the first EDD of a tetrasaccharide containing a sulfated hexuronic acid. For these more highly sulfated HS oligomers, alternative strategies are shown to be effective for extracting full structural details. These strategies include sodium cation replacement of protons for determining the sites of sulfation, and desulfation of the oligosaccharides for the generation of product ions for assigning uronic acid stereochemistry. (C) 2012 Elsevier B.V. All rights reserved.