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
Source PublicationANGEWANDTE CHEMIE-INTERNATIONAL EDITION
ISSN1433-7851
Volume57Issue:39Pages:12880-12885
Abstract

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.

KeywordAnticoagulants Drug Discovery Fucosylated Chondroitin Sulfate Glycosaminoglycans Oligosaccharides
DOI10.1002/anie.201807546
Language英语
WOS Research AreaChemistry
WOS SubjectChemistry, Multidisciplinary
WOS IDWOS:000444941600049
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Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/62428
Collection植物化学与西部植物资源持续利用国家重点实验室
Corresponding AuthorWu, Mingyi; Li, Zhongjun
Affiliation1.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
Recommended Citation
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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