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Development of pseudo-LOS vaccines

Research Project

Project/Area Number 10306022
Research Category

Grant-in-Aid for Scientific Research (A).

Allocation TypeSingle-year Grants
Section一般
Research Field Applied molecular and cellular biology
Research InstitutionTOTTORI UNIVERSITY

Principal Investigator

RYOHEI Yamasaki  Tottori University, Dept of Biochemistry & Biotechnology, Professor, 農学部, 教授 (80273887)

Co-Investigator(Kenkyū-buntansha) TSUYOSHI Sanekata  Tottori University, School of Agriculture, Associate Professor, 農学部, 助教授 (20205991)
KEN Nouda  Tottori University, School of Agriculture, Associate Professor, 農学部, 助教授 (60218287)
JUNICHI Tamura  Tottori University, School of Education & Regional Sciences, Associate Professor, 教育地域科学部, 助教授 (30221401)
HIROYUKI Koshino  Institute for Physical and Chemical Research, Division of Analysis of Molecular Structures, Senior Researcher, 分子構造解析室, 室長 (50321758)
黒野 定  理化学研究所, フロンティア研究システム, 研究員 (20271554)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥34,300,000 (Direct Cost: ¥34,300,000)
Fiscal Year 2000: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1999: ¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1998: ¥20,500,000 (Direct Cost: ¥20,500,000)
KeywordsLPS / Lipooligosaccharide (LOS / Neisseria gonorrhoeae / Vaccine / Oligosaccharide / LOS / リポ多糖 / ワクチン / エピトープ / 構造解析 / 免役化学 / オリゴ糖 / りん菌 / 免疫化学
Research Abstract

1) Determination of MAb 2C7-defined epitope and structural requirements for its epitope expression.
We found that the major LOS produced by strain WG is an elongated form of 15253 LOS ; a lactoneotetraose is linked to the Hep[1] and a lactose to the Hep[2], GlcNAc-(lactose)Hep[2]-(lactoneotetraose)Hep[1] and that 2) the minor LOS component is a N-acetylgalactosaminylated form of the major LOS component. Immunochemical analyses showed that the entire 15253 OS structure, GlcNAc-(lactose)Hep[2]-(lactose)Hep[1], is essential for expression of the 2C7 epitope. Also, some fatty acids in the lipid A moiety are important for the maximum expression of the epitope. In addition, we also disclosed that human sera contain an anti-LOS antibody whose specificity is similar to MAb 2C7. Our study shows that an epitope located close to the inner core could be potentially used as a safe and protective vaccine against N.gonorrhoeae.
2) Synthesis of the 15253 OS
We developed a new method to synthesize L-glycero-D-mannoheptoside in a semi-preparative scale (〜50g). We also synthesized heptoside derivatives which can be used as a donor or an acceptor. By using those derivatives, we found optimal conditions for glycosidation reactions to synthesize partial 15253 OS structures containing branched Hep structures. By synthesizing building blocks for the 15253 OS structure, we developed a strategy for the synthesis of the entire 15253 OS structure.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] K.Nabeta,K.Komuro,T.Utoh,H.Tazak and H.Koshino: "Biosynthesis of (-)- -Barabatene from 13C-and 2H-Labelled Acetate, Mevalonate and Glycerol"J.Chem.Soc.Chem.Commun.. 169-170 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] R.Yamasaki,H.Koshino,S.Kurono,Y.Nishinaka,D.McQillen,A.Kume,S.Gulati and P.A.Rice: "Structural and Immunochemical Characterization of a Neisseria gonorrhoeae Epitope Defined by a Monoclonal Antibody 2C7"J.Biol.Chem.. 274. 36550-36558 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] J.Tamura,Y.Miura and H.H.Freeze: "Synthesis of -GlcA (1 3)- -Gal and -CalNAc (1 4)- -GlcA (1 3)- -Gal as Biotinylated 2-Aminoethyl Glycosides and the Streptavidin Complex Formation"J.Carbohydr.Chem.. 18. 1-14 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Noda,K.Kubota and R.Yamasaki: "Separation of Lipooligosaccharides by Linear Gradient Gel Electrophoresis"Anal.Biochem. 279. 18-22 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Koshino,Y.Kono,K.Yoneyama and J.Uzawa: "^<15>N NMR Study of Toxoflavin and Fervenulin"Heterocycles. 52. 811-817 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] R.Yamasaki,A.Takajo,H.Kubo,M.Matsui,K.Ishii,Yoshida: "Convenient Synthesis of L-Glycero-D-Manno-Heptopyranoside"J.Carbohydr.Chem.. 20(in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Nabeta, K.Komuro, T.Utoh, H.Tazaki and H.Koshino: "Biosynthesis of (-)-β-Barabatene from ^<13>C- and ^2H-Labelled Acetate Mevalonate and Glycerol"J.Chem.Soc.Chem.Commun.. 169-170 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] R.Yamasaki, H.Koshino, S.Kurono, Y.Nishinaka, D.McQillen, A.Kume, S.Gulati and P.A.Rice: "Structural and Immunochemical Characterization of a Neisseria gonorrhoeae Epitope Defined by a Monoclonal Antibody 2C7"J.Biol.Chem.. 274. 36550-36558 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] J.Tamura, Y.Miura and H.H.Freeze: "Synthesis of β-GlcA(1→3)-β-Gal and α-GalNAc(1→4)-β-GlcA(1→3)-β-Gal as Biotinylated 2-Aminoethyl Glycosides and the Streptavidin Complex Formation"J.Carbohydr.Chem.. 18. 1-14 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Noda, K.Kubota and R.Yamasaki: "Separation of Lipooligosaccharides by Linear Gradient Gel Electrophoresis"Anal.Biochem.. 279. 18-22 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Koshino, Y.Kono, K.Yoneyama and J.Uzawa: "^<15>N NMR Study of Toxoflavin and Fervenulin"Heterocycles. 52. 811-817 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] R.Yamasaki, A.Takajo, H.Kubo, M.Matsui, K.Ishii, Yoshida: "Convenient Synthesis of L-Glycero-D-Manno-Heptopyranoside"J.Carbohydr.Chem.. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Nouda,K.Kubota and R.Yamasaki: "Separation of Lipooligosaccharides by Linear Gradient Gel Electrophoresis"Analytical Biochemitry. 279. 18-22 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] R.Yamasaki,A.Takajyo,H.Kubo,M.Matsui,K.Ishii,M.Yoshida: "Convenient Synthesis of L-Glycero-D-Manno-Heptopyranoside"J.Carbohydrate Chemistry. 20(印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Rhohei yamasaki: "Structural and immunochemical characterization of a Neisseria gonorrhoeae epitope defined by a monoclonal antibody 2C7;the antibody recognizes a conserved epitope on specific lipooligosaccharides in spite of the presence of human carbohydrate epitopes"J.Biol.Chem.. 274・51. 36550-36558 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ken Noda: "Separation of lipooligosaccharides by linear gradient gel electrophoresis"Anal.Biochem.. 279・1. 18-22 (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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