A Nanomolar Multivalent Ligand as Entry Inhibitor of the Hemagglutinin of Avian Influenza
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- 作者：Moritz Waldmann ; Raffael Jirmann ; Ken Hoelscher ; Martin Wienke ; Felix C. Niemeyer ; Dirk Rehders ; Bernd Meyer
- 刊名：Journal of the American Chemical Society
- 出版年：2014
- 出版时间：January 15, 2014
- 年：2014
- 卷：136
- 期：2
- 页码：783-788
- 全文大小：431K
- ISSN：1520-5126
文摘
Influenza virus attaches itself to sialic acids on the surface of epithelial cells of the upper respiratory tract of the host using its own protein hemagglutinin. Species specificity of influenza virus is determined by the linkages of the sialic acids. Birds and humans have 伪2鈥? and 伪2鈥? linked sialic acids, respectively. Viral hemagglutinin is a homotrimeric receptor, and thus, tri- or oligovalent ligands should have a high binding affinity. We describe the in silico design, chemical synthesis and binding analysis of a trivalent glycopeptide mimetic. This compound binds to hemagglutinin H5 of avian influenza with a dissociation constant of KD = 446 nM and an inhibitory constant of KI = 15 渭M. In silico modeling shows that the ligand should also bind to hemagglutinin H7 of the virus that causes the current influenza outbreak in China. The trivalent glycopeptide mimetic and analogues have the potential to block many different influenza viruses.