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
2018-09-24
发表期刊ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
ISSN1433-7851
卷号57期号:39页码:12880-12885
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.
关键词anticoagulants drug discovery fucosylated chondroitin sulfate glycosaminoglycans oligosaccharides
资助信息National Natural Science Foundation of China
DOI10.1002/anie.201807546
语种英语
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
WOS类目Chemistry, Multidisciplinary
WOS记录号WOS:000444941600049
出版者WILEY-V C H VERLAG GMBH
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/62428
专题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
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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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