Cryogenic Infrared Spectroscopy Reveals Structural Modularity in the Vibrational Fingerprints of Heparan Sulfate Diastereomers
Cryogenic Infrared Spectroscopy Reveals Structural Modularity in the Vibrational Fingerprints of Heparan Sulfate Diastereomers
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DOI：
10.1021/acs.analchem.0c02048
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发表时间：
2020-08-04
影响因子：
7.4
通讯作者：
Pagel, Kevin
中科院分区：
文献类型：
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作者：
Lettow, Maike;Grabarics, Marko;Pagel, Kevin
硫酸乙酰肝素和肝素是具有线性序列的高酸性多糖，由交替的葡糖胺和己糖醛酸结构单元组成。己糖醛酸单元的同一性显示出沿其序列的沿着的可变性，因为D-葡萄糖醛酸及其C5差向异构体L-艾杜糖醛酸都可以存在。由此产生的骨架多样性代表了通过基于质谱的技术进行明确结构分配的主要挑战。在这里，我们采用低温红外光谱质量选择离子，以克服这一挑战，并区分异构硫酸乙酰肝素四糖，不同的只是在其己糖醛酸结构单元的配置。在1000 ~ 1800 cm（-1）的指纹区域记录了一组系统的合成硫酸乙酰肝素立体异构体的高分辨率红外光谱。实验揭示了四个非对映异构体的光谱特征的特征组合的研究，并暗示在振动指纹的结构模块化。通过最先进的量子化学计算发现了强的光谱结构相关性并使其合理化。研究结果表明，低温红外光谱技术有可能扩展基于质谱的硫酸乙酰肝素和结构相关生物分子测序工具包。
Heparan sulfate and heparin are highly acidic polysaccharides with a linear sequence, consisting of alternating glucosamine and hexuronic acid building blocks. The identity of hexuronic acid units shows a variability along their sequence, as D-glucuronic acid and its C5 epimer, L-iduronic acid, can both occur. The resulting backbone diversity represents a major challenge for an unambiguous structural assignment by mass spectrometry-based techniques. Here, we employ cryogenic infrared spectroscopy on mass-selected ions to overcome this challenge and distinguish isomeric heparan sulfate tetrasaccharides that differ only in the configuration of their hexuronic acid building blocks. High-resolution infrared spectra of a systematic set of synthetic heparan sulfate stereoisomers were recorded in the fingerprint region from 1000 to 1800 cm(-1). The experiments reveal a characteristic combination of spectral features for each of the four diastereomers studied and imply structural modularity in the vibrational fingerprints. Strong spectrum-structure correlations were found and rationalized by state-of-the-art quantum chemical calculations. The findings demonstrate the potential of cryogenic infrared spectroscopy to extend the mass spectrometry-based toolkit for the sequencing of heparan sulfate and structurally related biomolecules.