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Structural analysis and anticoagulant activities of the novel sulfated fucan possessing a regular well-defined repeating unit from sea cucumber.
Mar Drugs. 2015 Apr 13; 13(4):2063-84.MD

Abstract

Sulfated fucans, the complex polysaccharides, exhibit various biological activities. Herein, we purified two fucans from the sea cucumbers Holothuria edulis and Ludwigothurea grisea. Their structures were verified by means of HPGPC, FT-IR, GC-MS and NMR. As a result, a novel structural motif for this type of polymers is reported. The fucans have a unique structure composed of a central core of regular (1→2) and (1→3)-linked tetrasaccharide repeating units. Approximately 50% of the units from L. grisea (100% for H. edulis fucan) contain sides of oligosaccharides formed by nonsulfated fucose units linked to the O-4 position of the central core. Anticoagulant activity assays indicate that the sea cucumber fucans strongly inhibit human blood clotting through the intrinsic pathways of the coagulation cascade. Moreover, the mechanism of anticoagulant action of the fucans is selective inhibition of thrombin activity by heparin cofactor II. The distinctive tetrasaccharide repeating units contribute to the anticoagulant action. Additionally, unlike the fucans from marine alga, although the sea cucumber fucans have great molecular weights and affluent sulfates, they do not induce platelet aggregation. Overall, our results may be helpful in understanding the structure-function relationships of the well-defined polysaccharides from invertebrate as new types of safer anticoagulants.

Authors+Show Affiliations

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. wumingyi@mail.kib.ac.cn.State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. xulib@mail.kib.ac.cn. School of Life Sciences, University of Chinese Academy of Sciences, Beijing 100000, China. xulib@mail.kib.ac.cn.State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. zhaolongyan@mail.kib.ac.cn. School of Life Sciences, University of Chinese Academy of Sciences, Beijing 100000, China. zhaolongyan@mail.kib.ac.cn.State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. xiaochuang@mail.kib.ac.cn. School of Life Sciences, University of Chinese Academy of Sciences, Beijing 100000, China. xiaochuang@mail.kib.ac.cn.State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. gaona@mail.kib.ac.cn. School of Life Sciences, University of Chinese Academy of Sciences, Beijing 100000, China. gaona@mail.kib.ac.cn.State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. luolanjya@sina.com.State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. yanglian@mail.kib.ac.cn.State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. lizi@mail.kib.ac.cn.Pharmacy Department, Yunnan University of TCM, Kunming 650200, China. chenlingyun@ynutcm.edu.cn.State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. Zhaojinhua@mail.kib.ac.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25871288

Citation

Wu, Mingyi, et al. "Structural Analysis and Anticoagulant Activities of the Novel Sulfated Fucan Possessing a Regular Well-defined Repeating Unit From Sea Cucumber." Marine Drugs, vol. 13, no. 4, 2015, pp. 2063-84.
Wu M, Xu L, Zhao L, et al. Structural analysis and anticoagulant activities of the novel sulfated fucan possessing a regular well-defined repeating unit from sea cucumber. Mar Drugs. 2015;13(4):2063-84.
Wu, M., Xu, L., Zhao, L., Xiao, C., Gao, N., Luo, L., Yang, L., Li, Z., Chen, L., & Zhao, J. (2015). Structural analysis and anticoagulant activities of the novel sulfated fucan possessing a regular well-defined repeating unit from sea cucumber. Marine Drugs, 13(4), 2063-84. https://doi.org/10.3390/md13042063
Wu M, et al. Structural Analysis and Anticoagulant Activities of the Novel Sulfated Fucan Possessing a Regular Well-defined Repeating Unit From Sea Cucumber. Mar Drugs. 2015 Apr 13;13(4):2063-84. PubMed PMID: 25871288.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural analysis and anticoagulant activities of the novel sulfated fucan possessing a regular well-defined repeating unit from sea cucumber. AU - Wu,Mingyi, AU - Xu,Li, AU - Zhao,Longyan, AU - Xiao,Chuang, AU - Gao,Na, AU - Luo,Lan, AU - Yang,Lian, AU - Li,Zi, AU - Chen,Lingyun, AU - Zhao,Jinhua, Y1 - 2015/04/13/ PY - 2015/01/26/received PY - 2015/03/25/revised PY - 2015/03/26/accepted PY - 2015/4/15/entrez PY - 2015/4/15/pubmed PY - 2015/12/31/medline SP - 2063 EP - 84 JF - Marine drugs JO - Mar Drugs VL - 13 IS - 4 N2 - Sulfated fucans, the complex polysaccharides, exhibit various biological activities. Herein, we purified two fucans from the sea cucumbers Holothuria edulis and Ludwigothurea grisea. Their structures were verified by means of HPGPC, FT-IR, GC-MS and NMR. As a result, a novel structural motif for this type of polymers is reported. The fucans have a unique structure composed of a central core of regular (1→2) and (1→3)-linked tetrasaccharide repeating units. Approximately 50% of the units from L. grisea (100% for H. edulis fucan) contain sides of oligosaccharides formed by nonsulfated fucose units linked to the O-4 position of the central core. Anticoagulant activity assays indicate that the sea cucumber fucans strongly inhibit human blood clotting through the intrinsic pathways of the coagulation cascade. Moreover, the mechanism of anticoagulant action of the fucans is selective inhibition of thrombin activity by heparin cofactor II. The distinctive tetrasaccharide repeating units contribute to the anticoagulant action. Additionally, unlike the fucans from marine alga, although the sea cucumber fucans have great molecular weights and affluent sulfates, they do not induce platelet aggregation. Overall, our results may be helpful in understanding the structure-function relationships of the well-defined polysaccharides from invertebrate as new types of safer anticoagulants. SN - 1660-3397 UR - https://www.unboundmedicine.com/medline/citation/25871288/Structural_analysis_and_anticoagulant_activities_of_the_novel_sulfated_fucan_possessing_a_regular_well_defined_repeating_unit_from_sea_cucumber_ DB - PRIME DP - Unbound Medicine ER -