Synthesis of Fucosylated Chondroitin Sulfate Nonasaccharide as a Novel Anticoagulant Targeting Intrinsic Factor Xase Complex | |
Zhang, Xiao1; Liu, Huiying1; Lin, Lisha2; Yao, Wang1; Zhao, Jinhua2; Wu, Mingyi2; Li, Zhongjun1 | |
刊名 | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION |
2018-09-24 | |
卷号 | 57期号:39页码:12880-12885 |
关键词 | Anticoagulants Drug Discovery Fucosylated Chondroitin Sulfate Glycosaminoglycans Oligosaccharides |
ISSN号 | 1433-7851 |
DOI | 10.1002/anie.201807546 |
英文摘要 | 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. |
资助项目 | National Natural Science Foundation of China[21472007] ; National Natural Science Foundation of China[21232002] ; National Natural Science Foundation of China[8167330] |
WOS研究方向 | Chemistry |
语种 | 英语 |
出版者 | WILEY-V C H VERLAG GMBH |
WOS记录号 | WOS:000444941600049 |
资助机构 | National Natural Science Foundation of China |
内容类型 | 期刊论文 |
源URL | [http://ir.kib.ac.cn/handle/151853/62428] |
专题 | 昆明植物研究所_植物化学与西部植物资源持续利用国家重点实验室 |
通讯作者 | Wu, Mingyi; Li, Zhongjun |
作者单位 | 1.Peking Univ, Sch Pharmaceut Sci, Dept Biol Chem, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China 2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West C, Kunming 650201, Yunnan, Peoples R China |
推荐引用方式 GB/T 7714 | Zhang, Xiao,Liu, Huiying,Lin, Lisha,et al. Synthesis of Fucosylated Chondroitin Sulfate Nonasaccharide as a Novel Anticoagulant Targeting Intrinsic Factor Xase Complex[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2018,57(39):12880-12885. |
APA | Zhang, Xiao.,Liu, Huiying.,Lin, Lisha.,Yao, Wang.,Zhao, Jinhua.,...&Li, Zhongjun.(2018).Synthesis of Fucosylated Chondroitin Sulfate Nonasaccharide as a Novel Anticoagulant Targeting Intrinsic Factor Xase Complex.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,57(39),12880-12885. |
MLA | Zhang, Xiao,et al."Synthesis of Fucosylated Chondroitin Sulfate Nonasaccharide as a Novel Anticoagulant Targeting Intrinsic Factor Xase Complex".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 57.39(2018):12880-12885. |
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