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首页> 外文期刊>Annual Review of Analytical Chemistry >Heparin Characterization: Challenges and Solutions
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Heparin Characterization: Challenges and Solutions

机译：肝素表征：挑战与解决方案

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摘要

Although heparin is an important and widely prescribed pharmaceutical anticoagulant, its high degree of sequence microheterogeneity and size poly-dispersity make molecular-level characterization challenging. Unlike nucleic acids and proteins that are biosynthesized through template-driven assembly processes, heparin and the related glycosaminoglycan heparan sulfate are actively remodeled during biosynthesis through a series of enzymatic reactions that lead to variable levels of O- and N-sulfonation and uronic acid epimers. As summarized in this review, heparin sequence information is determined through a bottom-up approach that relies on depolymerization reactions, size- and charge-based separations, and sensitive mass spectrometric and nuclear magnetic resonance experiments to determine the structural identity of component oligosaccharides. The structure-elucidation process, along with its challenges and opportunities for future analytical improvements, is reviewed and illustrated for a heparin-derived hexasaccharide.
机译：尽管肝素是一种重要且广泛使用的药物抗凝剂，但是其高度的序列微异质性和大小的多分散性使分子水平的表征面临挑战。与通过模板驱动的组装过程进行生物合成的核酸和蛋白质不同，肝素和相关的糖胺聚糖硫酸乙酰肝素在生物合成过程中会通过一系列酶促反应进行积极重塑，从而导致O-和N-磺化和糖醛酸差向异构体的水平发生变化。如本综述所述，肝素序列信息是通过自下而上的方法确定的，该方法依赖于解聚反应，基于大小和电荷的分离以及敏感的质谱和核磁共振实验来确定组分寡糖的结构特征。对肝素衍生的六糖的结构阐明过程及其挑战和未来分析改进的机会进行了综述和说明。

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