Synthesis of Fucosylated Chondroitin Sulfate Nonasaccharide as a Novel Anticoagulant Targeting Intrinsic Factor Xase Complex
Synthesis of Fucosylated Chondroitin Sulfate Nonasaccharide as a Novel Anticoagulant Targeting Intrinsic Factor Xase Complex
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岩藻糖化硫酸软骨素九糖作为靶向内在因子 Xase 复合物的新型抗凝剂的合成
DOI：
10.1002/anie.201807546
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Li Zhongjun
中科院分区：
文献类型：
--
作者：
Zhang Xiao;Liu Huiying;Lin Lisha;Yao Wang;Zhao Jinhua;Wu Mingyi;Li Zhongjun
岩藻糖基化硫酸软骨素（FuCS）是一种结构独特的糖胺聚糖，其寡糖具有优异的抗凝活性，不良反应和出血风险较低。在本文中，我们报告了一种基于软骨素的酶促降解在12个线性步骤的基础上合成FuCS六糖和九糖的简便方法。与临床上的低分子肝素药物依诺肝素相比，本研究合成的九糖通过与凝血因子IXa的高亲和力结合，显示出相似的APTT活性和选择性内源性凝血因子Xase复合物抑制活性（（12.9±0.83）nm），从而为开发针对内源性凝血途径的新型抗凝药物提供了希望。
Fucosylated chondroitin sulfate (FuCS) is a structurally distinct glycosaminoglycan, and its oligosaccharides exhibit excellent anticoagulant activity with lower risks of adverse effects and bleeding. Herein we report a facile approach to the synthesis of FuCS hexa‐ and nonasaccharides on the basis of the enzymatic degradation of chondroitin over 12 linear steps. As compared with a clinical low‐molecular‐weight heparin drug (enoxaparin), the nonasaccharide synthesized in this study displayed similar APTT activity and selective intrinsic factor Xase complex inhibitory activity ((12.9±0.83) nm) by binding to factor IXa with high affinity, thus offering promise for the development of new anticoagulant agents targeting the intrinsic coagulation pathway.