Affinity Research Of Multivalent DNA Tetrahedron Modified By Sialic Acid And Influenza A Virus Hemagglutinin

Influenza is one of the infectious diseases that endanger the health of human life.Studying of the infection and spread of influenza virus and then further blocking its infection are important means of treating influenza.Studies have shown that the influenza virus starts the infection process through multivalent binding of the hemagglutinin protein on the surface of virus and sialic acid receptor on the surface of epithelial cells,researchers tried to construct artificial multivalent sialic acid skeleton as inhibitor of virus,it inhibits influenza virus infection by competitively binding to hemagglutinin,but researchers still know very little about the details of multivalent binding between hemagglutinin and sialic acid,for example,the sialic acid configuration which have good affinity for binding to hemagglutinin,the best optimal spatial distribution of sialic acid,etc.,these unclear mechanisms limit the development and application of multivalent inhibitors.The programmability and precise addressability of DNA nanostructures make it have great potential as multivalent inhibitor molecular framework.Researchers can precisely regulate the spatial distribution of sialic acid on DNA nanostructures.Biocompatibility also makes it have great advantage in vivo applications.In this paper,we use DNA tetrahedral nanostructures as a multivalent framework to explore the multivalent effect of the influenza virus hemagglutinin binding to sialic acid,and try to explore the effect of the spatial distribution of sialic acid during this process.We first synthesized the sialic acid trisaccharide structure by combination of chemical and enzymatic methods,next we connected sialic acid to DNA single strand by click chemistry and then synthesized different valent of sialic acid modified DNA tetrahedral nanostructure and characterization of DNA tetrahedron using polyacrylamide gel electrophoresis(PAGE)and atomic force microscopy(AFM).Finally we quantitatively analyze the affinity between influenza virus hemagglutinin and DNA tetrahedron using microscale thermophoresis(MST).Results showed that the DNA tetrahedron structure get a very good affinity with influenza virus hemagglutinin.In brief,we constructed a multivalent functional platform modified by sialic acid based on DNA tetrahedron,this research have great significance in the in-depth understanding of the infection mechanism of influenza virus and development of new multivalent inhibitor.