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Synthesis of Fucosylated Chondroitin Sulfate Nonasaccharide as a Novel Anticoagulant Targeting Intrinsic Factor Xase Complex
Author(s) -
Zhang Xiao,
Liu Huiying,
Lin Lisha,
Yao Wang,
Zhao Jinhua,
Wu Mingyi,
Li Zhongjun
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201807546
Subject(s) - chemistry , chondroitin sulfate , chondroitin , heparin , anticoagulant drug , glycosaminoglycan , factor ixa , coagulation , sulfation , biochemistry , heparan sulfate , factor x , biophysics , combinatorial chemistry , stereochemistry , thrombin , platelet , psychology , psychiatry , biology , immunology
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) n m ) by binding to factor IXa with high affinity, thus offering promise for the development of new anticoagulant agents targeting the intrinsic coagulation pathway.