Marine Drugs
·
2024
·Vol. 22
·期 6
·265
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IF 4.9
Lige Cui,Huifang Sun,Xiaolei Shang,Jing Wen,Pengfei Li,Shengtao Yang,Linxia Chen,Xiangyang Huang,Haoyang Li,Ronghua Yin,Jinhua Zhao
Three polysaccharides (SnNG, SnFS and SnFG) were purified from the body wall ofStichopus naso. The physicochemical properties, including monosaccharide composition, molecular weight, sulfate content, and optical rotation, were analyzed, confirming that SnFS and SnFG are sulfated polysaccharides commonly found in sea cucumbers. The highly regular structure {3)-L-Fuc2S-(α1,}nof SnFS was determined via a detailed NMR analysis of its oxidative degradation product. By employing β-elimination depolymerization of SnFG, tri-, penta-, octa-, hendeca-, tetradeca-, and heptadeca-saccharides were obtained from the low-molecular-weight product. Their well-defined structures confirmed that SnFG possessed the backbone of {D-GalNAc4S6S-β(1,4)-D-GlcA}, and each GlcA residue was branched with Fuc2S4S. SnFS and SnFG are both structurally the simplest version of natural fucan sulfate and fucosylated glycosaminoglycan, facilitating the application of low-value sea cucumbersS. naso. Bioactivity assays showed that SnFG and its derived oligosaccharides exhibited potent anticoagulation and intrinsic factor Xase (iXase) inhibition. Moreover, a comparative analysis with the series of oligosaccharides solely branched with Fuc3S4Sshowed that in oligosaccharides with lower degrees of polymerization, such as octasaccharides, Fuc2S4Sled to a greater increase in APTT prolongation and iXase inhibition. As the degree of polymerization increases, the influence from the sulfation pattern diminishes, until it is overshadowed by the effects of molecular weight.
研究领域:
海洋生物化学
·
药理学
·
结构生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2017
·
IF 4.811
Lufeng Yan,Junhui Li,Danli Wang,Tian Ding,Yaqin Hu,Xingqian Ye,Robert J. Linhardt,Shiguo Chen
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 ( M w) 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 3 kDa. Meanwhile, human FXII activation and platelet aggregation were markedly reduced with decreasing M w and were moderate when under 12.0 kDa. Thus, fragments of 3–12.0 kDa should be safe and effective as selective inhibitors of intrinsic tenase complex for application as clinical anticoagulants.
研究领域:
海洋生物学
·
药理学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2013
·
IF 3.479
Longyan Zhao,Sensen Lai,Rong Huang,Mingyi Wu,Na Gao,Li Xu,Hongbo Qin,Wenlie Peng,Jinhua Zhao
Fucosylated glycosaminoglycans (FGs) are complex glycosaminoglycans that exhibit potent anticoagulant activity. To study the relationship between molecular size and biological activity, oligosaccharides with (2,5)-anhydro- d -talose units at new reducing ends were prepared by hydrazine deacetylation and nitrous acid depolymerization. The product chemical structures were analyzed by one- and two-dimensional NMR methods. Additionally, anticoagulant activities were evaluated by clotting assay and chromogenic substrate cleavage. The results demonstrated that under mild deacetylation and deaminative cleavage conditions, both products were relatively homogeneous and sulfated fucose branch types and sulfate substituents remained stable. These depolymerized FGs with different molecular sizes had potent intrinsic anticoagulant activities, which were similar to those that were obtained by free-radical depolymerization with similar molecular weights. Decreasing molecular weight may weaken activity but not significantly affect factor Xase and heparin cofactor II (HCII)-mediated thrombin inhibition.
研究领域:
生物化学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）