Zhang Xuedong, Yan Guangwei, Liu Xinming, Fu Jiewen, Shi Xiang, Cao Pei, Sun Yuqian, Zhong Shengping, Nong Jiale, Jiang Peiqi, Liu Yonghong, Zhang Baoshun, Yuan Qingxia, Zhao Longyan
Guangxi Key Laboratory of Marine Drugs, Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200, China.
College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
Mar Drugs. 2025 Feb 1;23(2):64. doi: 10.3390/md23020064.
The depolymerized products and oligosaccharide fractions from sea cucumber fucosylated glycosaminoglycans (FGs) are promising anticoagulant candidates, and more novel FG-derived oligosaccharides from low-priced sea cucumbers are expected to be obtained. This study isolated 5-12 oligomers (OF1-OF3) with unusual branches from β-eliminative depolymerized products of FG (CqFG). Detailed NMR analyses showed that OF1-OF3 consisted of a chondroitin 4,6-sulfates backbone and some sulfated fucosyl branches (FucS), including monosaccharides (α-l-Fuc, α-l-Fuc, α-l-Fuc, α-l-Fuc, and α-l-Fuc) and a disaccharide D-Gal-α1,3-l-Fuc with the ratio of ~36:35:10:7:3:9, attached to the C-3 position of β-d-GlcA or its derivatives, such as α-l-Δ4,5GlcA and β-d-GlcA-ol. Unusually, α-l-Fuc was the main FucS branch; no α-l-Fuc branch was found, and α-l-Fuc and α-l-Fuc branches were also found in OF1-OF3. The OF2 and OF3 could strongly inhibit the intrinsic and common coagulation pathways. Intrinsic FXase is a target of OF2 and OF3 inhibiting the intrinsic coagulation pathways, and the unusual side chains may increase the intrinsic FXase inhibitory activity. OF2 and OF3 showed negligible bleeding risk, and less bleeding than heparin (HP), low-molecular-weight heparins (LMWHs), and CqFG. These findings support novel FG oligosaccharides with some unusual branches from low-priced sea cucumbers to be prepared as safer anticoagulants.
海参岩藻糖基化糖胺聚糖(FGs)的解聚产物和低聚糖组分是很有前景的抗凝血候选物,有望从价格低廉的海参中获得更多新型的FG衍生低聚糖。本研究从FG(CqFG)的β-消除解聚产物中分离出5 - 12种具有异常分支的低聚物(OF1 - OF3)。详细的核磁共振分析表明,OF1 - OF3由硫酸软骨素4,6 - 硫酸酯主链和一些硫酸化岩藻糖基分支(FucS)组成,包括单糖(α - l - Fuc、α - l - Fuc、α - l - Fuc、α - l - Fuc和α - l - Fuc)和二糖D - Gal - α1,3 - l - Fuc,其比例约为36:35:10:7:3:9,连接在β - d - GlcA或其衍生物(如α - l - Δ4,5GlcA和β - d - GlcA - ol)的C - 3位上。不同寻常的是,α - l - Fuc是主要的FucS分支;未发现α - l - Fuc分支,且在OF1 - OF3中还发现了α - l - Fuc和α - l - Fuc分支。OF2和OF3能强烈抑制内源性和共同凝血途径。内源性FXase是OF2和OF3抑制内源性凝血途径的靶点,异常的侧链可能会增加内源性FXase抑制活性。OF2和OF3的出血风险可忽略不计,且比肝素(HP)、低分子肝素(LMWHs)和CqFG的出血少。这些发现支持将从价格低廉的海参中制备的具有一些异常分支的新型FG低聚糖作为更安全的抗凝血剂。