Synthesis of low-molecular weight fucoidan derivatives and their binding abilities to SARS-CoV-2 spike proteins
Synthesis of low-molecular weight fucoidan derivatives and their binding abilities to SARS-CoV-2 spike proteins
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DOI：
10.1039/d1md00264c
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发表时间：
2021-09-07
影响因子：
4.1
通讯作者：
Toshima, Kazunobu
中科院分区：
文献类型：
--
作者：
Koike, Tatsuki;Sugimoto, Aoi;Toshima, Kazunobu
设计并系统合成了岩藻依聚糖衍生物10-13，其基本糖链由具有不同硫酸化模式的重复α（1，4）连接的L-岩藻吡喃糖基残基组成。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。结果首次表明，10表现出最高的岩藻依聚糖衍生物的抑制活性。10的抑制活性远高于已报道的SARS-CoV-2S蛋白的配体磺达肝癸钠。此外，10对肝素与几种突变SARS-CoV-2 S蛋白的结合表现出抑制活性，但发现不抑制Xa因子（FXa）活性，否则可能导致不期望的抗凝活性。
Fucoidan derivatives 10-13, whose basic sugar chains are composed of repeating alpha(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.