4.8 Article

Synthesis of Fucosylated Chondroitin Sulfate Nonasaccharide as a Novel Anticoagulant Targeting Intrinsic Factor Xase Complex

Journal

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 57, Issue 39, Pages 12880-12885

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201807546

Keywords

anticoagulants; drug discovery; fucosylated chondroitin sulfate; glycosaminoglycans; oligosaccharides

Funding

  1. National Natural Science Foundation of China [21472007, 21232002, 8167330]

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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.

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