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

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.

• Authors: Xiao Zhang, Huiying Liu, Lisha Lin, Wang Yao, Jinhua Zhao, Mingyi Wu, Zhongjun Li
• Journal: Angewandte Chemie (International ed. in English) (Angew Chem Int Ed Engl) Vol. 57 Issue 39 Pg. 12880-12885 (09 24 2018) ISSN: 1521-3773 [Electronic] Germany
• PMID: 30067300 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Anticoagulants
• Factor Xa Inhibitors
• Glycosaminoglycans
• Oligosaccharides
• fucosylated chondroitin sulfate
• Chondroitin Sulfates
• Thrombin
• Factor Xa

Topics

• Anticoagulants (chemical synthesis, chemistry, metabolism)
• Chondroitin Sulfates (chemical synthesis, chemistry, metabolism)
• Factor Xa (chemistry, metabolism)
• Factor Xa Inhibitors (chemical synthesis, chemistry, metabolism)
• Glycosaminoglycans (chemistry)
• Humans
• Kinetics
• Oligosaccharides (chemistry, metabolism)
• Partial Thromboplastin Time
• Thrombin (chemistry, metabolism)
• Thrombin Time