Fucoidan derivatives 10–13, whose basic sugar chains are composed of repeating α(1,4)-linked L-fucopyranosyl residues with different sulfation patterns, were designed and systematically synthesized. A structure–activity relationship (SAR) study examined competitive inhibition by thirteen fucoidan derivatives against heparin binding to the SARS-CoV-2 spike (S) protein. The results showed for the first time that 10 exhibited the highest inhibitory activity of the fucoidan derivatives used. The inhibitory activity of 10 was much higher than that of fondaparinux, the reported ligand of SARS-CoV-2 S protein. Furthermore, 10 exhibited inhibitory activities against the binding of heparin with several mutant SARS-CoV-2 S proteins, but was found to not inhibit factor Xa (FXa) activity that could otherwise lead to undesirable anticoagulant activity.

中文翻译：

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低分子量褐藻糖胶衍生物的合成及其与 SARS-CoV-2 刺突蛋白的结合能力

设计并系统合成了岩藻依聚糖衍生物10-13，其基本糖链由重复的 α(1,4)-连接的L- fucopyranosyl 残基组成，具有不同的硫酸化模式。一项构效关系 (SAR) 研究检测了 13 种岩藻依聚糖衍生物对肝素与 SARS-CoV-2 刺突 (S) 蛋白结合的竞争性抑制作用。结果首次表明，10种在所用岩藻依聚糖衍生物中表现出最高的抑制活性。10的抑制活性远高于已报道的SARS-CoV-2 S蛋白配体磺达肝素。此外，10表现出对肝素与几种突变型 SARS-CoV-2 S 蛋白结合的抑制活性，但发现不抑制 Xa 因子（FXa）活性，否则会导致不良的抗凝活性。