By-Products of Heparin Production Provide a Diverse Source of Heparin-like and Heparan Sulfate Glycosaminoglycans.
By-Products of Heparin Production Provide a Diverse Source of Heparin-like and Heparan Sulfate Glycosaminoglycans.
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肝素生产的副产品提供了类肝素和硫酸乙酰肝素糖胺聚糖的多种来源。
DOI：
10.1038/s41598-019-39093-6
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发表时间：
2019
影响因子：
4.6
通讯作者：
Taylor SL
中科院分区：
文献类型：
--
作者：
Taylor SL
全球药用肝素(HP)的产量正在增加，而从粘膜原料生产的过程中会产生大量的废物副产品。这些化合物含有较低的硫酸盐化的类幽门螺杆菌和硫酸乙酰肝素(HS)，以及其他具有药用潜力的生物活性实体--糖胺聚糖。在这里，我们首次从标准肝素生产的四个主要副产物组分中分离纯化了类HP和HS多糖，并对其结构和功能进行了表征。通过双糖组成分析和核磁共振对副产物的分析表明，它们与HP有一系列不同的结构特征(特别是还原的硫酸盐和硫酸根双糖的含量)，而且它们都是不同的。纯化的副产物的功能性质各不相同，每一种在不同的检测中都显示出不同的抗凝血剂特性，并且都表现出比HP显著更低的对凝血途径的整体和特异性抑制。这些副产物保留了通过成纤维细胞生长因子受体信号促进细胞增殖的能力，它们之间只有微小的差异。这些综合分析表明，它们代表了一种结构多样的HP类和HS多糖的未开发和经济来源，具有加强未来结构活性研究和发现这些重要天然产物的新生物医学应用的潜力。
Global production of pharmaceutical heparin (Hp) is increasing, and the production process from raw mucosal material results in large amounts of waste by-products. These contain lower sulfated Hp-like and heparan sulfate (HS), as well as other glycosaminoglycans, which are bioactive entities with pharmaceutical potential. Here we describe the first purification, structural and functional characterisation of Hp-like and HS polysaccharides from the four major by-product fractions of standard heparin production. Analysis of the by-products by disaccharide composition analysis and NMR demonstrated a range of structural characteristics which differentiate them from Hp (particularly reduced sulfation and sulfated disaccharide content), and that they are each distinct. Functional properties of the purified by-products varied, each displaying distinct anticoagulant profiles in different assays, and all exhibiting significantly lower global and specific inhibition of the coagulation pathway than Hp. The by-products retained the ability to promote cell proliferation via fibroblast growth factor receptor signalling, with only minor differences between them. These collective analyses indicate that they represent an untapped and economical source of structurally-diverse Hp-like and HS polysaccharides with the potential for enhancing future structure-activity studies and uncovering new biomedical applications of these important natural products.