Synthesis and anticoagulation studies of "short-armed" fucosylated chondroitin sulfate glycoclusters
Synthesis and anticoagulation studies of "short-armed" fucosylated chondroitin sulfate glycoclusters
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“短臂”岩藻糖基化硫酸软骨素糖簇的合成及抗凝研究
DOI：
10.1016/j.carres.2018.07.008
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发表时间：
2018-09-01
影响因子：
3.1
通讯作者：
Li, Zhongjun
中科院分区：
文献类型：
--
作者：
Liu, Huiying;Zhang, Xiao;Li, Zhongjun
岩藻糖基化硫酸软骨素（FuCS）是一种存在于海参中的结构复杂的糖胺聚糖，具有广泛的生物活性，其中抗凝活性对于开发具有降低不良反应和出血风险的替代抗凝药物特别有吸引力。先前的研究表明，带有几个三糖表位的FuCS糖模拟物显示出有希望的抗凝活性，并且不改变FuCS的作用模式。为了简化高价糖簇的合成难度并获得相对较低分子量的候选化合物，本文报道了两个低价且结构更紧凑的FuCS糖簇的合成。抗凝研究表明，这些简化的“短臂”糖簇表现出与“长臂”高价糖簇相当的效力，为开发新型抗凝剂提供了一种简洁的方法。
Fucosylated chondroitin sulfate (FuCS) is a structurally complex glycosaminoglycan found in sea cucumbers with a wide spectrum of biological activities, among which anticoagulant activity is particularly attractive for the development of alternative anticoagulant drugs with decreased adverse effects and risks of bleeding. Previous studies show that FuCS glycomimetics bearing several trisaccharide epitopes displayed promising anticoagulant activity and did not change the mode of action of FuCS. To simplify synthetic difficulty of high valent glycoclusters and obtain candidate compounds with relatively low molecular weights, here we report the synthesis of two FuCS glycoclusters with low valence and more compact structures. Anticoagulation studies showed that these simplified "short-armed" glycoclusters demonstrated comparable potency with "long-armed" high valent glycoclusters, offering a concise approach for the development of novel anticoagulant agents.