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

文献类型：期刊论文

作者Liu, Yuanjie2; Li, Rongfeng3,4,5; Song, Lin1; Li, Kecheng3,4,5; Yu, Huahua3,4,5; Xing, Ronge3,4,5; Liu, Song3,4,5; Li, Pengcheng3,4,5
刊名INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
出版日期2024-06-01
卷号269页码:10
关键词Fucosylated chondroitin sulfate Sea cucumber Cucumaria frondosa Anticoagulant Bleeding risk Coagulation factor
ISSN号0141-8130
DOI10.1016/j.ijbiomac.2024.131952
通讯作者Li, Rongfeng(rongfengli@qdio.ac.cn) ; Song, Lin(03231@qust.edu.cn)
英文摘要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.
WOS关键词TENASE COMPLEX ; HEPARIN ; GLYCOSAMINOGLYCAN ; ANTIOXIDANT ; POLYSACCHARIDE
资助项目Natural Science Foundation of Nantong City[JC2023031] ; Key R & D Program of Shandong Province, China[2023CXGC010412] ; Key R & D Program of Shandong Province, China[2022CXGC020413] ; Natural Science Foundation of Shandong Province[ZR2022YQ37]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry ; Polymer Science
语种英语
WOS记录号WOS:001239927000001
出版者ELSEVIER
源URL[http://ir.qdio.ac.cn/handle/337002/186074]  
专题海洋研究所_实验海洋生物学重点实验室
通讯作者Li, Rongfeng; Song, Lin
作者单位1.Qingdao Univ Sci & Technol, Coll Marine Sci & Biol Engn, Qingdao 266042, Peoples R China
2.Qingdao Univ Sci & Technol, Coll Chem & Mol Engn, Qingdao 266042, Peoples R China
3.Chinese Acad Sci, Beijing, Peoples R China
4.Chinese Acad Sci, Inst Oceanol, Ctr Ocean Mega Sci, Shandong Prov Key Lab Expt Marine Biol, Qingdao 266071, Peoples R China
5.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Drugs & Bioprod, 1 Wenhai Rd, Qingdao 266237, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Yuanjie,Li, Rongfeng,Song, Lin,et al. Intermediate molecular weight -fucosylated chondroitin sulfate from sea cucumber Cucumaria frondosa is a promising anticoagulant targeting intrinsic factor IXa[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,2024,269:10.
APA Liu, Yuanjie.,Li, Rongfeng.,Song, Lin.,Li, Kecheng.,Yu, Huahua.,...&Li, Pengcheng.(2024).Intermediate molecular weight -fucosylated chondroitin sulfate from sea cucumber Cucumaria frondosa is a promising anticoagulant targeting intrinsic factor IXa.INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,269,10.
MLA Liu, Yuanjie,et al."Intermediate molecular weight -fucosylated chondroitin sulfate from sea cucumber Cucumaria frondosa is a promising anticoagulant targeting intrinsic factor IXa".INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 269(2024):10.

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来源：海洋研究所

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