Sulfated fuco-oligosaccharides from Acaudina leucoprocta: Structural characterization and anticoagulant activity.

IF 5.1 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic Chemistry Pub Date : 2026-10-05 Epub Date: 2026-08-13 DOI:10.1016/j.bioorg.2026.110307

Zhengwei Ying, Haroon Khan, Li Peipei, Huicheng Yang, Lingyan Wang, Manman Chen, Chunyu Niu, Syed Shams Ul Hassan, Yan Chen, Leifang Zhang, Yin Chen, Yanlei Yu

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引用次数: 0

Abstract

Sulfated fucans from sea cucumbers are potent anticoagulants, but their structural complexity has hindered understanding of their structure-activity relationship at the oligosaccharide level. Herein, we report the preparation, structural characterization, and anticoagulant evaluation of structurally defined sulfated fuco-oligosaccharides from the sea cucumber, Acaudina leucoprocta. Crude polysaccharides were fractionated by anion-exchange chromatography to obtain a fucan sulfate fraction (WS-0). Mild acid hydrolysis of WS-0 generated an oligosaccharide mixture, which was purified by sequential Bio-Gel P-2 and anion-exchange chromatography, yielding a series of oligosaccharide fractions with degrees of polymerization (DP) ranging from 1 to 9. Their structures were elucidated using ESI-MS, MS/MS, and 800 MHz NMR spectroscopy. Two structurally defined fuco-disaccharides were obtained: α-L-Fucp2S4S-(1 → 3)-α/β-L-Fucp (dWS0-4-0.14) and a mixture of α-L-Fucp2S-(1 → 3)-α/β-L-Fucp and α-L-Fucp4S-(1 → 3)-α/β-L-Fucp (dWS0-4-0.05). Among the oligosaccharide fractions, dWS0-3-1 (DP 3-6) exhibited the strongest anticoagulant activity, prolonging APTT to 47.4 ± 4.7 s and TT to 43.2 ± 1.0 s at 400 μg/mL, while showing minimal effect on PT. Comparative analysis revealed that both chain length and sulfation pattern co-determine anticoagulant potency, with 2,4-di-O-sulfation enabling shorter chains to inhibit thrombin. This study provided the first structural map of anticoagulant fuco-oligosaccharides from A. leucoprocta, identifying minimal structural motifs for activity and offering promising leads for developing novel antithrombotic agents.

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从白直桃中提取的硫酸酸化岩藻低聚糖：结构表征和抗凝血活性。

从海参中提取的硫酸化岩藻聚糖是一种有效的抗凝血剂，但其结构的复杂性阻碍了对其寡糖结构-活性关系的理解。在此，我们报道了从海参Acaudina leucoprocta中提取的硫酸酸化岩藻低聚糖的制备、结构表征和抗凝血性评价。采用阴离子交换色谱法对粗多糖进行分馏，得到硫酸富聚糖馏分（WS-0）。WS-0的温和酸水解生成低聚糖混合物，通过顺序Bio-Gel P-2和阴离子交换层析纯化，得到一系列聚合度（DP）在1到9之间的低聚糖组分。采用ESI-MS、MS/MS和800 MHz NMR对其结构进行了鉴定。得到两种结构明确的岩藻双糖：α-L-Fucp2S4S-(1→3)-α/β-L-Fucp （dWS0-4-0.14）和α-L-Fucp2S-(1→3)-α/β-L-Fucp和α-L-Fucp4S-(1→3)-α/β-L-Fucp （dWS0-4-0.05）的混合物。其中，dWS0-3-1 （dp3 -6）在400 μg/mL时抗凝血活性最强，APTT延长至47.4±4.7 s， TT延长至43.2±1.0 s，而对PT的影响最小。对比分析表明，链长和硫酸化模式共同决定了抗凝血效力，2,4-二o-硫酸化使链短抑制凝血酶。这项研究提供了第一个来自白原木犀草抗凝血的岩藻寡糖的结构图谱，确定了最小的结构基序，并为开发新的抗血栓药物提供了有希望的线索。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.