title: Novel thiosialosides tethered to metal nanoparticles as potent influenza A virus haemagglutinin blockers.
abstract: BACKGROUND
  The purpose of this study was to develop a new class of influenza A virus haemagglutinin (HA) blockers by tethering thiosialoside molecules to metal nanoparticles and producing glycoclusters that enhance the affinity of HA binding by N-acetylneuraminic acid.
  
  
  METHODS
  Oxygen of the glycoside bond of sialoside was replaced with sulfur to prevent hydrolytic digestion of the N-acetylneuraminic acid residue by viral neuraminidase. Two novel thiosialosides, α-2-S-[p-(N-levulinyl)aminophenyl]-5-N-acetylneuraminic acid (Neu5Ac-S-Lev) and α-2-S-[m-(N-levulinyl)aminobenzyl]-5-N-acetylneuraminic acid (Neu5Ac-S-CH2-Lev), were tethered onto the surface of metal nanoparticles via an aminooxy functionalized thiol linker in a glycoblotting reaction. Gold (Au) and silver (Ag) nanoparticles were coated simultaneously with 11-mercaptoundecyl phosphorylcholine to reduce non-specific adsorption of proteins. Phosphorylcholine self-assembled monolayer-coated metals displaying clustered Neu5Ac (Neu5Ac-PCSAM-Au and Neu5Ac-PCSAM-Ag) were subjected to haemagglutination inhibition (HI) assays using the influenza A virus strain A/PR/8/1934 (H1N1).
  
  
  RESULTS
  Glyconanoparticles with thiosialosides had potent HI activities. In particular, Neu5Ac-PCSAM-Au with a diameter of 20 nm corresponding to 9.8 μM monosaccharide Neu5Ac was the most potent HA inhibitor. The versatility of this strategy was demonstrated by similar submicromolar HI activities of Neu5Ac-PCSAM-Ag with diameters of 50 nm and 150 nm.
  
  
  CONCLUSIONS
  Glycosylated metal nanoparticles were designed and synthesized as potent influenza A virus HA blockers. This study may contribute to the acceleration of the discovery of a new class of nanoparticle anti-influenza drugs.
authors: Division of Drug Discovery Research, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
authors: Fei
authors: F
authors: Feng
authors: Yoshihiro
authors: Y
authors: Sakoda
authors: Tatsuya
authors: T
authors: Ohyanagi
authors: Noriko
authors: N
authors: Nagahori
authors: Hitomi
authors: H
authors: Shibuya
authors: Masatoshi
authors: M
authors: Okamastu
authors: Nobuaki
authors: N
authors: Miura
authors: Hiroshi
authors: H
authors: Kida
authors: Shin-Ichiro
authors: S
authors: Nishimura
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000187:drug effects*; D009980:Influenza A virus / Q000187:drug effects* / Q000378:metabolism; D053768:Metal Nanoparticles; D012794:Sialic Acids / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D012794:Sialic Acids