title: Synthesis of multivalent sialyllactosamine-carrying glyco-nanoparticles with high affinity to the human influenza virus hemagglutinin.
abstract: A series of multivalent sialoglyco-conjugated nanoparticles were efficiently synthesized by using highly-branched α-glucuronic acid-linked cyclic dextrins (GlcA-HBCD) as a backbone. The sialoglycoside-moieties, with varying degrees of substitution, could be incorporated onto the preformed nanoparticles. These synthesized particles, which are highly soluble in aqueous solution, were shown to have a spherical nanostructure with a diameter of approximately 15nm. The interactions of the sialoglyco-nanoparticles (Neu5Acα2,6LacNAc-GlcA-HBCDs) with human influenza virus strain A/Beijing/262/95 (H1N1) were investigated using a hemagglutination inhibition assay. The sialoglyco-nanoparticle, in which the number of sialic acid substitution is 30, acted as a powerful inhibitor of virus binding activity. We show that both distance and multiplicity of effective ligand-virus formation play important roles in enhancing viral inhibition. Our results indicate that the GlcA-HBCD backbone can be used as a novel spherical nanocluster material for preparing a variety of glyco-nanoparticles to facilitate molecular recognition.
authors: Department of Chemistry and Biochemistry, National Institute of Technology, Fukushima College, 30 Nagao, Iwaki, Fukushima 970-8034, Japan. Electronic address: ogata@fukushima-nct.ac.jp.
authors: Makoto
authors: M
authors: Ogata
authors: Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, Japan.
authors: Seiichiro
authors: S
authors: Umemura
authors: Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, Japan.
authors: Naohiro
authors: N
authors: Sugiyama
authors: Department of Chemistry and Biochemistry, National Institute of Technology, Fukushima College, 30 Nagao, Iwaki, Fukushima 970-8034, Japan.
authors: Natsuki
authors: N
authors: Kuwano
authors: Department of Chemistry and Biochemistry, National Institute of Technology, Fukushima College, 30 Nagao, Iwaki, Fukushima 970-8034, Japan.
authors: Ami
authors: A
authors: Koizumi
authors: Department of General Education, National Institute of Technology, Fukushima College, 30 Nagao, Iwaki, Fukushima 970-8034, Japan.
authors: Tadakazu
authors: T
authors: Sawada
authors: Institute of Health Sciences, Ezaki Glico Co., Ltd, 4-6-5 Utajima, Nishiyodogawa, Osaka 555-8502, Japan.
authors: Michiyo
authors: M
authors: Yanase
authors: Institute of Health Sciences, Ezaki Glico Co., Ltd, 4-6-5 Utajima, Nishiyodogawa, Osaka 555-8502, Japan.
authors: Takeshi
authors: T
authors: Takaha
authors: Department of Chemistry, Biotechnology, and Chemical Engineering, Graduate School of Science and Engineering, Kagoshima University, 1-21-40 Korimoto, Kagoshima 890-0065, Japan.
authors: Jun-Ichi
authors: JI
authors: Kadokawa
authors: Integrated Bioscience Research Division, Graduate School of Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, Japan.
authors: Taichi
authors: T
authors: Usui
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D003912:Dextrins / Q000737:chemistry / Q000494:pharmacology; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000378:metabolism; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry; D009844:Oligosaccharides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D003912:Dextrins; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009844:Oligosaccharides; C062923:N-acetylneuraminosyl(alpha2-6)lactosamine; D020723:Glucuronic Acid; D019158:N-Acetylneuraminic Acid
keywords: Carbohydrate; Cluster effect; Influenza virus; Multivalency; Nanoparticle