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    Fucosylated chondroitin sulfate 9-18 oligomers exhibit molecular size-independent potent antithrombotic activity during circulating in the blood

    Author
    Yan, L.; Wang, D.; Yu, Y.; Zhang, F.; Ye, X.; Linhardt, Robert J.; Chen, S.
    ORCID
    https://orcid.org/0000-0003-2219-5833
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    Other Contributors
    Date Issued
    2020
    Subject
    Biology; Chemistry and chemical biology; Chemical and biological engineering; Biomedical engineering
    Degree
    Terms of Use
    In Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/;
    Full Citation
    Fucosylated chondroitin sulfate 9-18 oligomers exhibit molecular size-independent potent antithrombotic activity during circulating in the blood, L. Yan, D. Wang, Y. Yu, F. Zhang, X. Ye, R. J. Linhardt, S. Chen, ACS Chemical Biology, 15, 2232-2246, 2020.
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    URI
    https://doi.org/10.1021/acschembio.0c00439; https://hdl.handle.net/20.500.13015/5485
    Abstract
    Fucosylated chondroitin sulfate (FCS) oligosaccharides extracted from sea cucumber and depolymerized exhibit potent anticoagulant activity. Knowledge of the antithrombotic activity of different size oligosaccharides and their fucose (Fuc) branch sulfation pattern should promote their development for clinical applications. We prepared highly purified FCS trisaccharide repeating units from hexasaccharide (6-mer) to octadecasaccharide (18-mer), including those with 2,4-disulfated and 3,4-disulfated Fuc branches. All 10 oligosaccharides were identified by their nuclear magnetic resonance structures and ESI-FTMS spectroscopy. In vitro anticoagulant activities and surface plasmon resonance binding tests indicated those of larger molecular sizes and 2,4-disulfated Fuc branches showed stronger anticoagulant effects with respect to anti-FXase activity, as well as stronger binding to FIXa among various clotting proteins. However, both types of FCS 9-mer to 18-mer exhibited molecular size-independent potent antithrombotic activity in vivo at the same dose. In addition, both types of the FCS 6-mer exhibited favorable antithrombotic activity in vivo, although they showed weak anticoagulant activity in vitro. Combining absorption and metabolism studies, we conclude that FCS 9-18 oligomers could remain in the circulation to interact with various clotting proteins to prevent thrombus formation, and appreciable quantities of these oligomers could be excreted through the kidneys. All FCS 9-18 oligomers also resulted in no bleeding, hypotension, or platelet aggregation risk during blood circulation. Thus, FCS 9-18 oligomers with 2,4-disulfated or 3,4-disulfated Fuc branches exhibit potent and safe antithrombotic activity needed for clinical applications.;
    Description
    ACS Chemical Biology, 15, 2232-2246; Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
    Department
    The Linhardt Research Labs.; The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS);
    Relationships
    The Linhardt Research Labs Online Collection; Rensselaer Polytechnic Institute, Troy, NY; https://harc.rpi.edu/;
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    https://login.libproxy.rpi.edu/login?url=https://doi.org/10.1021/acschembio.0c00439;
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