Tang Shengchang, Puryear Wendy B, Seifried Brian M, Dong Xuehui, Runstadler Jonathan A, Ribbeck Katharina, Olsen Bradley D
Department of Chemical Engineering, ‡Department of Biological Engineering, and §Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
Department of Chemical Engineering, Department of Biological Engineering, and §Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
ACS Macro Lett. 2016 Mar 15;5(3):413-418. doi: 10.1021/acsmacrolett.5b00917. Epub 2016 Mar 7.
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.
通过无保护基团的开环易位聚合反应合成了在侧链末端含有α-2,6-连接唾液酸的仿生刷状聚合物。聚合物通过唾液酸苷的多价呈现表现出菌株选择性抗病毒活性。通过独立改变聚合度、唾液酸的数量密度和刷状聚合物中侧链的长度，进一步控制了多价效应。优化三维唾液酸苷间距以更好地结合血凝素三聚体对于增强多价效应和通过血凝抑制试验和体外感染试验确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，这些刷状聚合物可用作模型系统来剖析天然粘蛋白中复杂的设计原则。
