Investigation of the biological functions of heparan sulfate using a chemoenzymatic synthetic approach.

Investigation of the biological functions of heparan sulfate using a chemoenzymatic synthetic approach.
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DOI:
10.1039/d0cb00199f
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发表时间:
2021-02-22
影响因子:
4.1
通讯作者:
Liu J
Liu J
中科院分区:
其他
文献类型:
--
作者:
Wang Z;Arnold K;Dhurandhare VM;Xu Y;Liu J

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硫酸乙酰肝素(HS)是一种高度硫酸化的多糖,在动物界发挥着重要的生理和病理生理作用。肝素是HS的一种高度硫酸化形式,是一种广泛使用的抗凝药物。从生物来源中分离,肝素和HS都是具有不同糖链长度和硫酸化模式的多糖混合物。HS的结构异质性使HS相关生物活性的研究复杂化。结构确定的HS寡糖的可用性对于理解糖结构对功能的贡献至关重要。化学酶法合成HS低聚糖是一种经济有效的方法。结构确定的寡糖现在已被生物学家广泛使用。本文综述了近年来利用这种新的合成方法开发新的抗凝治疗药物以及发现HS在病理条件下对肝损伤的保护作用。该合成方法还允许我们制备参考糖标准品以改进HS的结构分析。硫酸乙酰肝素(HS)是一种高度硫酸化的多糖,在动物界发挥着重要的生理和病理生理作用。
Heparan sulfate (HS) is a highly sulfated polysaccharide playing essential physiological and pathophysiological roles in the animal kingdom. Heparin, a highly sulfated form of HS, is a widely used anticoagulant drug. Isolated from biological sources, both heparin and HS are polysaccharide mixtures with different sugar chain lengths and sulfation patterns. Structural heterogeneity of HS complicates the investigation of HS-related biological activities. The availability of structurally defined HS oligosaccharides is critical in understanding the contribution of saccharide structures to the functions. The chemoenzymatic synthetic approach is emerging as a cost-effective method to synthesize HS oligosaccharides. Structurally defined oligosaccharides are now widely available for biologists. This review summarizes our efforts in using this new synthetic method to develop new anticoagulant therapeutics and discover the role of HS to protect liver damage under pathological conditions. The synthetic method also allows us to prepare reference saccharide standards to improve structural analysis of HS. Heparan sulfate (HS) is a highly sulfated polysaccharide playing essential physiological and pathophysiological roles in the animal kingdom.