Chemoenzymatic synthesis of heparan sulfate and heparin oligosaccharides and NMR analysis: paving the way to a diverse library for glycobiologists.
Chemoenzymatic synthesis of heparan sulfate and heparin oligosaccharides and NMR analysis: paving the way to a diverse library for glycobiologists.
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硫酸乙酰肝素和肝素寡糖的化学酶促合成和NMR分析：为糖生物学家的多样化库铺平道路。
DOI：
10.1039/c7sc03541a
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发表时间：
2017-12-01
期刊：
影响因子：
8.4
通讯作者：
Linhardt RJ
中科院分区：
文献类型：
--
作者：
Zhang X;Pagadala V;Jester HM;Lim AM;Pham TQ;Goulas AMP;Liu J;Linhardt RJ
采用化学酶法合成了一系列硫酸肝素（HS）寡糖，并用核磁共振对其进行了系统研究。硫酸乙酰肝素（HS）是糖胺聚糖（GAG）家族的一员，在动物源的生物过程中起着重要作用。肝素是一种高硫酸盐形式的HS，在世界范围内广泛用作抗凝血药物。HS和肝素的高度多样性和复杂性是结构表征和生物活性研究的障碍。获得结构明确的低聚糖对于HS和肝素结构-活性关系的成功发展至关重要。本研究通过一种高效的化学酶合成方法，制备了66种不同磺化模式和大小的HS和肝素低聚糖文库。首先对文库中的每一个低聚糖进行了系统的核磁共振波谱研究。除了不同寡糖的可用性外，本工作还提供了有助于表征更复杂多糖结构的光谱数据，为确保药物肝素的质量提供了保障。构建的HS/肝素文库可用于活性筛选和今后的构效关系研究。
A library of diverse heparan sulfate (HS) oligosaccharides was chemoenzymatically synthesized and systematically studied using NMR. Heparan sulfate (HS) is a member of the glycosaminoglycans (GAG) family that plays essential roles in biological processes from animal sources. Heparin, a highly sulfated form of HS, is widely used as anticoagulant drug worldwide. The high diversity and complexity of HS and heparin represent a roadblock for structural characterization and biological activity studies. Access to structurally defined oligosaccharides is critical for the successful development of HS and heparin structure–activity relationships. In this study, a library of 66 HS and heparin oligosaccharides covering different sulfation patterns and sizes was prepared through an efficient method of chemoenzymatic synthesis. A systematic nuclear magnetic resonance spectroscopy study was firstly undertaken for every oligosaccharide in the library. In addition to the availability of different oligosaccharides, this work also provides spectroscopic data helpful for characterizing more complicated polysaccharide structures providing a safeguard to ensure the quality of the drug heparin. This HS/heparin library will be useful for activity screening and facilitate future structure–activity relationship studies.
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