Program of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil.
University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil.
Mar Drugs. 2018 Aug 30;16(9):304. doi: 10.3390/md16090304.
The anticoagulant and antithrombotic properties of three structurally correlated sea urchin-derived 3-linked sulfated α-glycans and their low molecular-weight derivatives were screened comparatively through various in vitro and in vivo methods. These methods include activated partial thromboplastin time, the inhibitory activity of antithrombin over thrombin and factor Xa, venous antithrombosis, the inhibition of platelet aggregation, the activation of factor XII, and bleeding. While the 2-sulfated fucan from was observed to be poorly active in most assays, the 4-sulfated fucan from , the 2-sulfated galactan from and their derivatives showed multiple effects. All marine compounds showed no capacity to activate factor XII and similar low bleeding tendencies regardless of the dose concentrations used to achieve the highest antithrombotic effect observed. The 2-sulfated galactan showed the best combination of results. Our work improves the background about the structure-function relationship of the marine sulfated glycans in anticoagulation and antithrombosis. Besides confirming the negative effect of the 2-sulfated fucose and the positive effect of the 2-sulfated galactose on anticoagulation in vitro, our results also demonstrate the importance of this set of structural requirements on antithrombosis in vivo, and further support the involvement of high-molecular weight and 4-sulfated fucose in both activities.
三种结构相关的海胆来源 3 连接硫酸化α-聚糖及其低分子量衍生物的抗凝和抗血栓特性通过各种体外和体内方法进行了比较筛选。这些方法包括活化部分凝血活酶时间、抗凝血酶对凝血酶和因子 Xa 的抑制活性、静脉抗血栓形成、血小板聚集抑制、因子 XII 的激活和出血。虽然 中的 2-硫酸化岩藻聚糖在大多数测定中活性较差，但 中的 4-硫酸化岩藻聚糖、 中的 2-硫酸化半乳糖聚糖及其衍生物表现出多种作用。所有海洋化合物都没有激活因子 XII 的能力，并且无论使用何种剂量浓度来达到观察到的最高抗血栓作用，出血倾向都相似且较低。2-硫酸化半乳糖聚糖显示出最佳的综合效果。我们的工作改善了海洋硫酸化聚糖在抗凝和抗血栓形成中的结构-功能关系的背景。除了证实 2-硫酸化岩藻糖在体外抗凝中的负面作用和 2-硫酸化半乳糖在体外抗凝中的正面作用外，我们的结果还表明，这组结构要求在体内抗血栓形成中的重要性，并进一步支持高分子量和 4-硫酸化岩藻糖在这两种活性中的参与。
