Molecular size is important for the safety and selective inhibition of intrinsic factor Xase for fucosylated chondroitin sulfate

Authors
Yan, Lufeng
Li, Junhui
Wang, Danli
Ding, Tian
Hu, Yaqin
Ye, Xingqian
Linhardt, Robert J.
Chen, Shiguo
ORCID
https://orcid.org/0000-0003-2219-5833
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Other Contributors
Issue Date
2017-12-15
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
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Full Citation
Molecular size is important for the safety and selective inhibition of intrinsic factor Xase for fucosylated chondroitin sulfate, L. Yan, J. Li, D. Wang, D. Tian, Y. Hu, X. Ye, R. J. Linhardt, S. Chen, Carbohydrate Polymers, 178, 180-189, 2017.
Abstract
Fucosylated chondroitin sulfate from sea cucumber Isostichopus badionotus (FCS-Ib) showed potent anticoagulant activities without selectivity. The present study focused on developing safe FCS-Ib oligomers showing selective inhibition of intrinsic factor Xase (anti-FXase) prepared through partial N-deacetylation-deaminative cleavage. The N-deacetylation degree was regulated by reaction time, controlling the resulting oligomer distribution. Structure analysis confirmed the selectivity of degradation, and 12 high purity fractions with trisaccharide-repeating units were separated. In vitro anticoagulant assays indicated a decrease in molecular weight (Mw) dramatically reduced activated partial thromboplastin time (APTT), thrombin time (TT), AT-dependent anti-FIIa and anti-FXa activities, while the oligomers retained potent anti-FXase activity until they fell below 3kDa. Meanwhile, human FXII activation and platelet aggregation were markedly reduced with decreasing Mw and were moderate when under 12.0kDa. Thus, fragments of 3-12.0kDa should be safe and effective as selective inhibitors of intrinsic tenase complex for application as clinical anticoagulants.
Description
Carbohydrate Polymers, 178, 180-189
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Carbohydrate Polymers
https://harc.rpi.edu/
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https://login.libproxy.rpi.edu/login?url=https://doi.org/10.1016/j.carbpol.2017.09.034