Antiviral Agents from Multivalent Presentation of Sialyl Oligosaccharides on Brush Polymers
Antiviral Agents from Multivalent Presentation of Sialyl Oligosaccharides on Brush Polymers
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DOI：
10.1021/acsmacrolett.5b00917
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发表时间：
2016-03-01
影响因子：
7.015
通讯作者：
Olsen, Bradley D.
中科院分区：
文献类型：
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作者：
Tang, Shengchang;Puryear, Wendy B.;Olsen, Bradley D.
采用无保护基团开环复分解聚合法制备了侧链末端含有α -2,6链唾液酸的仿生刷状聚合物。聚合物显示菌株选择性抗病毒活性，通过多价呈递。通过独立改变聚合程度、唾液酸的数量密度和刷状聚合物侧链的长度，进一步控制了多价效应。优化三维涎苷间距以更好地与血凝素三聚体结合，对于提高多价效应和血凝抑制实验和体外感染实验测定的抗病毒活性至关重要。利用它们与天然粘蛋白的结构相似性，这些刷状聚合物可以作为模型系统来剖析天然粘蛋白中复杂的设计原理。
Bioinspired brush polymers containing alpha-2,6-linked sialic acids at the side chain termini were synthesized by protection-group-free, ring-opening metathesis polymerization. Polymers showed strain-selective antiviral activity through multivalent presentation of the sialosides. The multivalent effect was further controlled by independently varying the degree of polymerization, the number density of sialic acids, and the length of side chains in the brush polymers. Optimizing the three-dimensional sialoside spacing for better binding to hemagglutinin trimers was of critical importance to enhance the multivalent effect and the antiviral activity determined by hemagglutination inhibition assays and in vitro infection assays. By taking advantage of their structural similarities with native mucins, these brush polymers can be used as model systems to dissect the intricate design principles in natural mucins.