Intermediate molecular weight -fucosylated chondroitin sulfate from sea cucumber Cucumaria frondosa is a promising anticoagulant targeting intrinsic factor IXa

Thromboembolic diseases pose a serious risk to human health worldwide. Fucosylated chondroitin sulfate (FCS) is reported to have good anticoagulant activity with a low bleeding risk. Molecular weight plays a significant role in the anticoagulant activity of FCS, and FCS smaller than octasaccharide i...

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Bibliographic Details
Published in:International Journal of Biological Macromolecules
Main Authors: Liu, Yuanjie, Li, Rongfeng, Song, Lin, Li, Kecheng, Yu, Huahua, Xing, Ronge, Liu, Song, Li, Pengcheng
Format: Report
Language:English
Published: ELSEVIER 2024
Subjects:
Fucosylated chondroitin sulfate
Sea cucumber
Cucumaria frondosa
Anticoagulant
Bleeding risk
Coagulation factor
Biochemistry & Molecular Biology
Chemistry
Polymer Science
Applied
TENASE COMPLEX
HEPARIN
GLYCOSAMINOGLYCAN
ANTIOXIDANT
POLYSACCHARIDE
Online Access:http://ir.qdio.ac.cn/handle/337002/186074
http://ir.qdio.ac.cn/handle/337002/186075
https://doi.org/10.1016/j.ijbiomac.2024.131952
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Summary:Thromboembolic diseases pose a serious risk to human health worldwide. Fucosylated chondroitin sulfate (FCS) is reported to have good anticoagulant activity with a low bleeding risk. Molecular weight plays a significant role in the anticoagulant activity of FCS, and FCS smaller than octasaccharide in size has no anticoagulant activity. Therefore, identifying the best candidate for developing novel anticoagulant FCS drugs is crucial. Herein, native FCS was isolated from sea cucumber Cucumaria frondosa (FCS c f ) and depolymerized into a series of lower molecular weights (FCS cf s). A comprehensive assessment of the in vitro anticoagulant activity and in vivo bleeding risk of FCS c f s with different molecule weights demonstrated that 10 kDa FCS cf (FCS cf -10 K) had a greater intrinsic anticoagulant activity than low molecular weight heparin (LMWH) without any bleeding risk. Using molecular modeling combined with experimental validation, we revealed that FCS cf -10 K can specifically inhibit the formation of the Xase complex by binding the negatively charged sulfate group of FCS cf -10 K to the positively charged side chain of arginine residues on the specific surface of factor IXa. Thus, these data demonstrate that the intermediate molecular weight FCS cf -10 K is a promising candidate for the development of novel anticoagulant drugs.

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