Synthesis And Anti Influenza Activity Study Of S-Linked Sialoside Conjugates

In this study,we have synthesized effective influenza virus inhibitors based on a vital factor that sialic acid is a natural receptor of influenza virus.Sialic acid was used as the initial reactant for the structural modification.First,we have increased the binding affinity of a single sialic acid unit by introducing an amine/guanidine group at the 4 position of sialic acid.Then,replacing the O-linked with an S-linked makes the ligand more robust and stable resistance to neuramindase(NA)cleavage.Two new types of small molecules were synthesized.We have chosen S-linked sialosides as modification molecules to carry out multivalent modification.We chose natural proteins present in plasma(Human Serum Albumin,HSA)as the scaffolds to synthesize BCN-HSA because of their availability,nontoxicity and nonimmunogenicity.Two kinds of sialic acid protein conjugates were synthesized via copper-freed catalytic "Click" reaction.The loading number of sialosides was determined by MALDI-TOF-MS.Moreover,using the poly(methyl vinyl ether-alt-maleic anhydride)as the backbone we have synthesized glycopolymer.The loading number of molecules was determined by size exclusion chromatography(SEC).we perform the fluorescent MUNANA-based NA inhibition assay against three influenza virus[A/HuNan/SWL1331/2014(H1N1),A/HuairouBeijing/11069/2014(H3N2),A/Chicken/Beijing/AT609/2014(H9N2)].Our results suggest that higher valency of sialosides and modification on the structure of sialic acid monomer might be required for achieving higher NA inhibitory activity.The poly conjugates has good antiviral activity at the cellular level.All of multivalent conjugates are not cytotoxic with concentrations up to 100 μM.Synthetic congugates is an effective influenza virus inhibitor with great research prospects and could be used for future research and development of anti-influenza virus drugs in this theme.