Functional design of artificial mucin based Influenza virus Inhibitor in overcoming the mutation

• Project/Area Number: 19310141
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: Shizuoka University
• Principal Investigator: USUI Taiichi Shizuoka University, 農学部, 教授 (50111802)
• Co-Investigator(Kenkyū-buntansha): MURATA Takeomi 静岡大学, 農学部, 准教授 (30273171) ; PARK Enoch 静岡大学, 創造科学技術大学院, 教授 (90238246) ; SUZUKI Takashi 静岡県立大学, 薬学部, 教授 (20240947) ; HIDARI Kazuya 静岡県立大学, 薬学部, 准教授 (20260226)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2009: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2008: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2007: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: 糖鎖工学 / 人工ムチン / インフルエンザウイルス / 複合糖質 / 分子認識 / 糖鎖ミメティックス / Glycotechnology / Influenza virus / Glycomimetics / Artificial mucin / Molcular design / Glycomaterial / Chemoenzymatic synthesis / Glycoconjugate / Influcnza virus

Research Abstract

インフルエンザウイルスの感染、接着に関わる特定の受容体シアロオリゴ糖鎖を高い効率且つ単純な手法で高密度に天然素材ポリペプチドである納豆菌由来γ-ポリグルタミン酸ベースに配して抗原性の変異を克服しかつトリ型およびヒト型インフルエンザウイルスに対応した強力な抗インフルエンザウイルス剤を構築した。また、感染阻害試験の結果から両型の受容体糖鎖特異性は末端シアル酸の結合様式において異なるだけでなく、そのコアとなる内部糖鎖構造も活性に大きく関与していることを実証した。

Research Products

• [Journal Article] Novel and facile synthesis of furanodictines A and B based on transformation of 2-acetamido-2-deoxy-Dglucose into 3, 6-anhydro hexofuranoses. (2010)
  • Author(s): Ogata, M., Hattori, T., Takeuchi, R., Usui, T
  • Journal Title: Carbohydr. Res 345 Pages: 230-234
  • Peer Reviewed
• [Journal Article] Molecular design of N-linked tetravalent glycosides bearing N-acetylglucosamine, N, N'-dicetylchitobiose and N-acetyllactosamine: Analysis of crosslinking activities with specific lectins. (2010)
  • Author(s): Masaka, R., Ogata, M., Misawa, Y., Yano M., Hashimoto, C., Murata, T., Kawagishi, H., Usui, T
  • Journal Title: Bioorg. Med. Chem 18 Pages: 621-629
  • Peer Reviewed
• [Journal Article] Molecular design of N-linked tetravalent glycosides bearing N-acetyl-glucosamine, N,N'-diacetylchitobiose and N-acetyllactosamine (2010)
  • Author(s): Ryuichi Masaka
  • Journal Title: Bioorganic Medicinal Chemistry 18 Pages: 621-629
  • Peer Reviewed
• [Journal Article] Structural analysis of the recognition mechanism of poly-Nacetyllactosamine by the human galectin-9 N-terminal carbohydrate recognition domain. (2009)
  • Author(s): Nagae, M., Nishi, N., Murata, T., Uusi, T., Nakamura, T
  • Journal Title: Glycobiology 19 Pages: 112-117
  • Peer Reviewed
• [Journal Article] Chemoenzymatic synthesis of sialoglycopolypeptides as glycomimetics to block infection by avian and human influenza virus. (2009)
  • Author(s): Ogata, M., Hidari, K., Murata, T., Shimada, S., Kozaki, W., Park, E.Y., Suzuki, T., Usui, T
  • Journal Title: Bioconjugate Chem 20 Pages: 538-549
  • Peer Reviewed
• [Journal Article] Moelcular design of spacer N-linked sialoglycopolypeptide as polymeric inhibitors against influenza virus infection. (2009)
  • Author(s): Ogata, M., Hidari, K., Kozaki, K., Murata, T., Hiratake, J., Park, E.Y., Suzuki, T., Usui, T
  • Journal Title: Biomacromolecules 10 Pages: 1894-1903
  • Peer Reviewed
• [Journal Article] Synthesis of sialoglycopolypeptide for potentially blocking influenza virus using a ratα2, 6-sialyltransferase expressed in BmNPV bacmid-injected silkworm larvae. (2009)
  • Author(s): Ogata, M., Nakajima, M., Kato, T., Obara, T., Yagi, H., Kato, K., Usui, T., Park, E. Y
  • Journal Title: BMC Biotechnol 9 Pages: 1-13
  • Peer Reviewed
• [Journal Article] Membrane microdomains from early gastrula embryos of medaka, Oryzias, are a platform of E-cadherin-and carbohydrate-mediated cell-cell interactions during epibody (2009)
  • Author(s): Tomoko Adachi
  • Journal Title: Glycoconjugate Journal 26 Pages: 285-299
  • Peer Reviewed
• [Journal Article] Chemoenzymatic synthesis of sialoglycopeptides as glycomimetics to block infection by avian and human influenza virus (2009)
  • Author(s): Makoto Ogata
  • Journal Title: Bioconjugate Chemistry 20 Pages: 538-549
  • Peer Reviewed
• [Journal Article] Molecular design of spacer N-linked sialoglycopolypeptide as polymeric inhibitors against influenza virus infection (2009)
  • Author(s): Makoto Ogata
  • Journal Title: Biomacromolecules 10 Pages: 1894-1903
  • Peer Reviewed
• [Journal Article] Synthesis of sialoglycopolypeptide for potentially blocking influenza virus using a rat a2, 6-sialyltransferase expressed in BmNPV bacmid-injected silkworm larvae (2009)
  • Author(s): Makoto Ogata
  • Journal Title: BMC Biotecnology 9 Pages: 1-13
  • Peer Reviewed
• [Journal Article] Chemoenzymatic synthesis of sialoglycopolypeptides as glycomimetics to block infection by avian human influenza viruses (2009)
  • Author(s): Makoto Ogata
  • Journal Title: Bioconjugate Chemistry 20 Pages: 538-549
  • Peer Reviewed
• [Journal Article] Structuial analysis of the recognition mechanism of poly-N-acetyllactosamine by the human galectin-9 N-terminal carbohydrate recognition domain (2009)
  • Author(s): Masamichi Nagae
  • Journal Title: Glycobiology 19 Pages: 112-117
  • Peer Reviewed
• [Journal Article] Enzymatic synthesis of spacer-linked divalent carrying N-acetylglucosamine and N-acetyllactosamine: Analysis of cross-linking activities with WGA. (2008)
  • Author(s): Misawa, Y., Akimoto, T., Amarume, S., Murata, T., Usui, T
  • Journal Title: J. Biochem 143 Pages: 21-30
  • Peer Reviewed
• [Journal Article] Efficient synthesis of spacer-N-limked double-headed glycosides N-acetylglucosamine and N, N'-diacetylchitobiose their cross-linking activities with wheat germ agglutinin. (2008)
  • Author(s): Misawa, Y., Masaka, R., Maeda, K., Yano, M., Murata, T., Kawagishi, H., Usui, T
  • Journal Title: Carbohydr. Res 347 Pages: 434-442
  • Peer Reviewed
• [Journal Article] characterization and application of glycopolymers carrying lactosamine repeats as entry inhibitors against influenza virus infection. (2008)
  • Author(s): Hidari, K., Murata, T., Yoshida, K., Takahashi, Y., Minamijima, Y., Miwa, Y., Adachi, S., Ogata, M., Usui, T., Suzuki, Y., Suzuki, T. Chemoenzymatic synthesis
  • Journal Title: Glycobiology 18 Pages: 779-788
  • Peer Reviewed
• [Journal Article] Chemoenzymatic synthesis, characterization and application of glycopolymers carrying lactosamine repeats as enhy inhibitors against influenza virus infection (2008)
  • Author(s): Kazuya IPJ Hidari
  • Journal Title: Glycobiology 18 Pages: 779-788
  • Peer Reviewed
• [Journal Article] Efficient synthesis of spacer-N-limked double-headed glycosides N-acetylglucosamine and N, N'-diacetylcliitobiose their cross-linking activities with wheat germ agglutinin (2008)
  • Author(s): Yoshinori Misawa
  • Journal Title: Carbohydrate Research 347 Pages: 434-442
  • Peer Reviewed
• [Journal Article] Enzymatic synthesis of spacer-linked divalent canying N-acetylglucosamine and N-acetyllactosamine : Anlysis of cross-linking activities with WGA (2008)
  • Author(s): Yoshinori Misawa
  • Journal Title: Journal of Biochemistry 143 Pages: 21-30
  • Peer Reviewed
• [Journal Article] Enzymatic synthesis of spacer-linked divalent glycosides carrying N-acetylglucosamine and N- acetyllactosamine:analysis of cross-linking activities with WGA (2008)
  • Author(s): Yoshitomo Misawa
  • Journal Title: J.Biochem. 141 Pages: 21-30
  • Peer Reviewed
• [Journal Article] Efficient synthesis of spacer-N-linked double headed glycosides carrying N-acetylglucosamine and N, N'-diacetylchitobiose and their cross-linkingactivities with wheat germ agglutinin (2008)
  • Author(s): Yoshitomo Misawa
  • Journal Title: Carbohydr. Res. 343 Pages: 434-442
  • Peer Reviewed
• [Journal Article] Chemoenzymatic synthesis of artificial glycopolypeptides containing multivalent sialyloligosaccharides with aγ-polyglutamic acid backbone and their effect for inhibition of infection by influenza viruses. Bioorg. (2007)
  • Author(s): Ogata, M., Murata, T., Murakami, K., Suzuki, T., Hidari, K., Suzuki, Y., Uusi, T
  • Journal Title: Med. Chem 15 Pages: 1383-1393
  • Peer Reviewed
• [Journal Article] Substrate specificity of N-acetylhexosaminidase from Aspergillus oryzae to artificialglycosyl acceptors having various substituents at the reducing ends. (2007)
  • Author(s): Ogata, M., Zeng, X., Uusi, T., Uzawa, H
  • Journal Title: Carbohydr. Res 342 Pages: 23-30
  • Peer Reviewed
• [Journal Article] Substrate specificity of N-acetylhexosaminidase from Aspergilllus oryzae to artificial glycosyl acceptors having various substituents at the reducing ends (2007)
  • Author(s): Makoto Ogata
  • Journal Title: Carbohydr. Res. 342 Pages: 23-30
  • Peer Reviewed
• [Journal Article] Chemoenzymatic synthesis of artifisial glycopeptides containing multi-valent sialyloligosaccharides with a γ-polygulutamic acid backbone and their effect on inhibition of infection by influenza (2007)
  • Author(s): Makoto Ogata
  • Journal Title: Bioorg. Med. Chem 15 Pages: 1383-1393
  • Peer Reviewed
• [Journal Article] Monovalent Gb3-/Gb2-derivatives conjugated with a phosphatidyl residue:A novel class of shiga toxin-neutralizing agent (2007)
  • Author(s): Paola Neri
  • Journal Title: Biol. Pharm. Bull. 30 Pages: 1697-1701
  • Peer Reviewed
• [Presentation] インフルエンザウイルス感染阻止剤の効率的合成と機能解析 (2009)
  • Author(s): 尾形慎
  • Organizer: 日本生化学会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2009-10-23
• [Presentation] 酵素-化学合成法を用いた人工糖鎖ポリペプチドの分子設計～酵素利用の観点から～ (2009)
  • Author(s): 尾形慎, 村田健臣, 朴龍洙, 碓氷泰市
  • Organizer: 糖質関連酵素シンポジウム
  • Place of Presentation: 弘前
  • Year and Date: 2009-09-18
• [Presentation] 酵素化学合成法を用いた人工糖鎖ポリペプチドの分子設計と～酵素利用の観点から～ (2009)
  • Author(s): 尾形慎
  • Organizer: 日本応用糖質科学会
  • Place of Presentation: 弘前大学
  • Year and Date: 2009-09-18
• [Presentation] シアロ型多価配糖体の設計とレクチンとの相互作用解析 (2009)
  • Author(s): 矢野恵美, 橋本知佳, 尾形慎, 朴龍洙, 村田健臣, 碓氷泰市
  • Organizer: 第29回日本糖質学会
  • Place of Presentation: 高山
  • Year and Date: 2009-09-10
• [Presentation] α2, 6シアル酸転移酵素の活性測定に対する受容体としての蛍光標識受容体基質の合成 (2009)
  • Author(s): 小原平圭, 尾形慎, 中馬康志, 朴龍洙, 村田健臣, 碓氷泰市
  • Organizer: 第29回日本糖質学会
  • Place of Presentation: 高山
  • Year and Date: 2009-09-10
• [Presentation] N-結合型糖鎖をミミックした二本鎖及び二分岐二本鎖配糖体の酵素・化学合成 (2009)
  • Author(s): 中馬康志, 小原平圭, 尾形慎, 村田健臣, 碓氷泰市
  • Organizer: 第29回日本糖質学会
  • Place of Presentation: 高山
  • Year and Date: 2009-09-10
• [Presentation] N-結合型糖鎖をミミックした二本鎖及び二分岐二本鎖配糖体の酵素化学合成 (2009)
  • Author(s): 中馬康志
  • Organizer: 日本糖質学会
  • Place of Presentation: 飛騨世界生活文化センター
  • Year and Date: 2009-09-10
• [Presentation] 糖鎖を活用した人工ムチンの設計と機能解析 (2009)
  • Author(s): 碓氷泰市
  • Organizer: 日本農芸化学会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2009-03-29
• [Presentation] ヒト及びトリインフルエンザウイルスに対する糖鎖ポリペプチド阻害剤としの高効率合成 (2009)
  • Author(s): 尾形慎
  • Organizer: 日本農芸化学会
  • Place of Presentation: 福岡
  • Year and Date: 2009-03-29
• [Presentation] ヒトおよびトリインフルエンザウイルス阻害剤としての人工糖鎖ポリペプチドの効率的合成 (2008)
  • Author(s): 小崎渉, 尾形慎, 朴龍洙, 村田健臣, 左一八, 鈴木隆, 碓氷泰市
  • Organizer: 第28回日本糖質学会
  • Place of Presentation: つくば
  • Year and Date: 2008-08-19
• [Presentation] 糖鎖を活用したインフルエンザウイルス感染阻害剤の機能設計 (2008)
  • Author(s): 尾形慎, 左一八, 島田静美, 小崎渉, 朴龍洙, 村田健臣, 碓氷泰市, 鈴木隆
  • Organizer: 第28回日本糖質学会
  • Place of Presentation: つくば
  • Year and Date: 2008-08-18
• [Presentation] 糖鎖を活用したインフルエンザウイルス感染阻害剤の機能設計 (2008)
  • Author(s): 尾形慎
  • Organizer: 日本糖質学会
  • Place of Presentation: 筑波
  • Year and Date: 2008-08-18
• [Presentation] ヒト及びトリインフルエンザウイルス阻害剤としての人工糖鎖ポリペプチドの高効率合成 (2008)
  • Author(s): 小崎渉
  • Organizer: 日本糖質学会
  • Place of Presentation: 筑波
  • Year and Date: 2008-08-18
• [Presentation] トリおよびヒトインフルエンザウイルスに対する糖鎖高分子阻害剤の分子設計(1) (2008)
  • Author(s): 小崎渉, 尾形慎, 酒井有子, 朴龍洙, 村田健臣, 左一八, 鈴木隆, 碓氷泰市
  • Organizer: 日本農芸化学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-03-28
• [Presentation] トリおよびヒトインフルエンザウイルスに対する糖鎖高分子阻害剤の分子設計(2) (2008)
  • Author(s): 尾形慎, 酒井有子, 小崎渉, 朴龍洙, 村田健臣, 島田静美, 左一八, 鈴木隆, 碓氷泰市
  • Organizer: 日本農芸化学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-03-28
• [Presentation] 抗インフルエンザウイルス剤の実践的合成法の開発 (2007)
  • Author(s): 小崎渉, 尾形慎, 朴龍洙, 村田健臣, 左一八, 鈴木隆, 碓氷泰市
  • Organizer: 第27回日本糖質学会
  • Place of Presentation: 福岡
  • Year and Date: 2007-08-02
• [Presentation] インフルエンザウイルス感染阻害剤としてのシアロ人工糖鎖ポリペプチドの分子設計 (2007)
  • Author(s): 尾形慎, 高橋香元, 朴龍洙, 村田健臣, 吉田和弘, 島田静美, 左一八, 鈴木隆, 碓氷泰市
  • Organizer: 第27回日本糖質学会
  • Place of Presentation: 福岡
  • Year and Date: 2007-08-02
• [Presentation] インフルエンザウイルス感染阻害剤としてのシアロ人工糖鎖ポリペプチドの分子設計 (2007)
  • Author(s): 尾形 慎
  • Organizer: 日本糖質学会
  • Place of Presentation: 福岡
  • Year and Date: 2007-08-01
• [Presentation] 抗インフルエンザ剤としてのLacNAc繰り返し含有シアロ糖鎖ポリペプチドの分子設計 (2007)
  • Author(s): 尾形慎, 朴龍洙, 村田健臣, 島田静美, 左一八, 鈴木隆, 碓氷泰市
  • Organizer: 日本農芸化学会
  • Place of Presentation: 東京
  • Year and Date: 2007-03-26
• [Presentation] 人工糖鎖ポリペプチドのスペーサー部構造の違いがインフルエンザウイルス感染阻害活性へ及ぼす影響 (2007)
  • Author(s): 酒井有子, 尾形慎, 村田健臣, 左一八, 鈴木隆, 碓氷泰市
  • Organizer: 日本農芸化学会
  • Place of Presentation: 東京
  • Year and Date: 2007-03-26
• [Book] Convenient synthesis of glycan-related oligosaccharides and their transformation into neoglycoconjugates using enzymatic methods. In: Experimental Glycoscience, Glycobiology. Taniguchi, N., Suzuki, A., et al.(eds.) (2008)
  • Author(s): Murata, T., Usui, T
  • Publisher: Springer
• [Book] Experimental Glycoscience, Glycobiology (Part1 Glycosyltransferase gene, Section 1 Glycosyltransferase) "Convenient synthesis of glycan-related oligosaccharides and their transformation into neoglycoconjugates using enzymatic methods. " (2008)
  • Author(s): Takeomi Murata, Taichi Usui
  • Publisher: Springer
• [Patent(Industrial Property Rights)] ウイルス阻害剤 (2010)
  • Inventor(s): 碓氷泰市, 尾形慎, 朴龍洙, 宮崎忠昭
  • Industrial Property Rights Holder: 国立大学法人静岡大学
  • Industrial Property Number: 2010-248463
  • Filing Date: 2010-03-04
• [Patent(Industrial Property Rights)] 新規なN結合型人工シアロ糖鎖含有ポリマーおよびその製造方法 (2008)
  • Inventor(s): 碓氷泰市, 村田健臣, 鈴木隆, 左一八, 大場勇介, 浜本智樹, 野口利忠
  • Industrial Property Rights Holder: 国立大学法人静岡大学,静岡県公立大学法人,ヤマサ醤油(株)
  • Filing Date: 2008-06-24
• [Patent(Industrial Property Rights)] 新規なN結合型人工シアロ糖鎖含有ポリマーおよびその製造方法 (2008)
  • Inventor(s): 碓氷泰市, 村田健臣, 左 一八, 鈴木 隆, 野口利忠
  • Industrial Property Rights Holder: 静岡大学, 静岡県立大学, ヤマサ醤油(株)
  • Filing Date: 2008-06-24
  • Overseas
• [Patent(Industrial Property Rights)] 抗ウイルス剤 (2007)
  • Inventor(s): 鈴木隆, 左一八, 村田健臣, 碓氷泰市, 竹田聡, 山田浩平, 野口利忠, 鈴木康夫
  • Industrial Property Rights Holder: 国立大学法人静岡大学,静岡県公立大学法人,ヤマサ醤油(株)
  • Industrial Property Number: 2007-161257
  • Filing Date: 2007-06-19
• [Patent(Industrial Property Rights)] 改変ポリヘドリンプロモーター、パクミド変異体及び目的タンパク質の製造方法 (2007)
  • Inventor(s): 朴龍洙, 碓氷泰市, 村田健臣, 金政真
  • Industrial Property Rights Holder: 国立大学法人静岡大学
  • Industrial Property Number: 2007-161257
  • Filing Date: 2007-06-11
• [Patent(Industrial Property Rights)] 新規なN結合型人工糖鎖含有ポリマーおよびその製造法 (2007)
  • Inventor(s): 碓氷 泰市、村田 健臣、鈴木 隆、左一 八、大庭 勇介、浜本 智樹、野口 利忠
  • Industrial Property Rights Holder: 静岡大学、静岡県、ヤマサ醤油(株)
  • Industrial Property Number: 2007-170079
  • Filing Date: 2007-06-28