State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China; University of Chinese Academy of Sciences, Beijing, China.
College of Pharmacy and Chemistry, Dali University, Dali, China.
Carbohydr Polym. 2015;127:427-37. doi: 10.1016/j.carbpol.2015.04.002. Epub 2015 Apr 10.
Fucosylated chondroitin sulfate (FCS) from sea cucumber with complex structure has potent anticoagulant activity by inhibition of intrinsic tenase; however, it could activate factor XII and platelet. To obtain FCS' fragments with selective inhibition on intrinsic tenase, a method for β-eliminative depolymerization of FCS was developed by treating FCS benzyl esters with alkaline in anhydrous solution. Our results demonstrated that the glycosidic linkages of GalNAc-β1, 4-GlcA were selectively cleaved and distinctive Δ(4,5) unsaturated hexuronic acid was formed at non-reducing end of resulting fragments, while the main structures were essentially stable during depolymerization. By this method, five depolymerized fragments (dFCSs) with various molecular sizes were prepared and their anticoagulant activities and activation activities of factor XII and platelet were compared. Overall, dFCSs with Mw 3.2-8.8 kDa reserved potent anticoagulant activities by inhibition of intrinsic tenase, and activation activities of factor XII or platelet could be diminished or eliminated.
岩藻糖基硫酸软骨素（FCS）具有复杂的结构，它通过抑制内源性凝血酶而具有很强的抗凝活性；然而，它也可以激活因子 XII 和血小板。为了获得对内在凝血酶具有选择性抑制作用的 FCS 片段，通过用碱性在无水溶液中处理 FCS 苄酯，开发了一种 FCS 的β消除解聚方法。我们的结果表明，GalNAc-β1,4-GlcA 的糖苷键被选择性切割，并且在所得片段的非还原端形成独特的 Δ(4,5) 不饱和六糖醛酸，而主要结构在解聚过程中基本稳定。通过这种方法，制备了五种具有不同分子量的解聚片段（dFCS），并比较了它们的抗凝活性以及对因子 XII 和血小板的激活活性。总体而言，Mw 为 3.2-8.8 kDa 的 dFCS 通过抑制内源性凝血酶保留了很强的抗凝活性，并且可以减少或消除对因子 XII 或血小板的激活活性。
