Antiviral Agents from Multivalent Presentation of Sialyl Oligosaccharides on Brush Polymers

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• 作者：Shengchang Tang ; Wendy B. Puryear ; Brian M. Seifried ; Xuehui Dong ; Jonathan A. Runstadler ; Katharina Ribbeck ; Bradley D. Olsen
• 刊名：ACS Macro Letters
• 出版年：2016
• 出版时间：March 15, 2016
• 年：2016
• 卷：5
• 期：3
• 页码：413-418
• 全文大小：408K
• ISSN：2161-1653

文摘

Bioinspired brush polymers containing α-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.