Highly purified fucosylated chondroitin sulfate oligomers with selective intrinsic factor Xase complex inhibition

Yan, Lufeng
Wang, D.
Zhu, Mengshan
Yu, Yanlei
Zhang, Fuming
Ye, Xingqian
Linhardt, Robert J.
Chen, Shiguo
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Highly purified fucosylated chondroitin sulfate oligomers with selective intrinsic factor Xase complex inhibition, L. Yan, D. Wang, M. Zhu, Y. Yu, F. Zhang, X. Ye, R. J. Linhardt, S. Chen, Carbohydrate Polymers,222, 115025, 2019.
Fucosylated chondroitin sulfate (FCS) oligosaccharides of specific molecular weight have shown potent anticoagulant activities with selectivity towards intrinsic factor Xase complex. However, the preparation of FCS oligosaccharides by traditional methods requires multiple purification steps consuming large amounts of time and significant resources. The current study focuses on developing a method for the rapid preparation of FCS oligomers from sea cucumber Pearsonothuria graeffei having 6-18 saccharide residues. The key steps controlling molecular weight (Mw) and purity of these FCS oligomers were evaluated. Structural analysis showed the resulting FCS oligomers were primarily l-Fuc3,4diS-α1,3-d-GlcA-β1,3-(d-GalNAc4,6diS-β1,4-[l-Fuc3,4diS-α1,3-]d-GlcA-β1,3-)nd-anTal-ol4,6diS (n = 1˜5) accompanied by partial de-fucosylation and/or de-sulfation. In vitro and in vivo experiments demonstrate that these FCS oligomers selectively inhibit intrinsic factor Xase complex and exhibit remarkable antithrombotic activity without hemorrhagic and hypotension side effects. This method is suitable for large-scale preparation of FCS oligosaccharides as clinical anticoagulants.
Carbohydrate Polymers,222, 115025
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Carbohydrate Polymers