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Development of oligosaccharide conjugates that could be potentially utilized as vaccines against pathogenic Gram-negative bacteria

Research Project

Project/Area Number 14360207
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied molecular and cellular biology
Research InstitutionTottori University

Principal Investigator

YAMASAKI Ryohei  Tottori University, Faculty of Agriculture, Professor, 農学部, 教授 (80273887)

Co-Investigator(Kenkyū-buntansha) ICHIYANAGI Tsuyoshi  Tottori University, Faculty of Agriculture, Lecturer, 農学部, 講師 (00302240)
ESUMI Yasuaki  The Institute of Physical and Chemical Research, Senior Research Associate, 分子構造解析室, 先任技師 (70087500)
KOMASE Katsuhiro  Kitasato University, Research Center for Biologicals, Head of Development Division, 生物製剤研究所・開発研究部門, 部門長(研究職) (80215384)
田村 純一  鳥取大学, 教育地域科学部, 助教授 (30221401)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2004: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2003: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥5,600,000 (Direct Cost: ¥5,600,000)
KeywordsLipooligosaccharide / Lipopolysaccharide / Oligosaccharide / Vaccine / Gram-negative bacteria / Human antibodies / Epitope / lipooligosaccharide / lipopolysacchride / oligosaccharide / vaccine / Neisseria / リポオリゴ糖 / リポ多糖 / オリゴ糖鎖 / グリコシル化 / 抗体 / エピトープ
Research Abstract

The object of this research is to study the possibility to develop carbohydrate vaccines t against pathogenic Gram-negative bacteria. We accomplished the following during the funding period.
1)Synthesis of branched core oligosaccharide(OS) expressed in 15253 LOS and OS conjugates. 15253 We developed a new heptose (Hep) intermediate, 3-O-silyl-Hep, for the synthesis of the core OS. By utilizing the Hep intermediate, we constructed the following branched core OS : the 2,3-,3,4-branched, and 2,3;3,4-dibranched structures. We also developed a basic strategy to synthesize OS conjugates using a model OS. Finally, we synthesize a-spacer KDO side by stereoselective anomeric O-acylation.
2)Analysis of antibodies specific for the core OS and the immunogenicity of a model OS conjugate. We characterized several antibodies that are specific for the core OS and showed that those core OS structures are immunogenic in humans for the first time, We also developed a sensitive western blot assay that would allow the detection of LOS (femt mol level) with lower concentration of antibodies and used this assay for the analysis of specificities of the above antibodies and anti-sera raised using the model OS conjugate.
Thus, we established a methodology for the synthesis of branched core OS and have shown that such core OS can be utilized for the development of vaccines against pathogenic Gram-negative bacteria.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (24 results)

All 2005 2004 2003 2002 Other

All Journal Article (15 results) Publications (9 results)

  • [Journal Article] Normal human sera contain bactericidal IgG that binds to the oligosaccharide epitope expressed within lipooligosaccharides of Neisseria gonorrhoeae2005

    • Author(s)
      H.Kubo, K.Ishii, H.Koshino, K.Toubetto, K.Naruchi, R.Yamasaki
    • Journal Title

      J.Biochem.(Tokyo) 137

      Pages: 487-494

    • NAID

      10017344557

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Normal human sera contain bactericidal IgG that binds to the oligosaccharide epitope expressed within lipooligosaccharides of Neisseria gonorrhoeae2005

    • Author(s)
      R.Yamasaki, T.Maruyama, U.Yabe, S.Asuka
    • Journal Title

      J Biochem (Tokyo) 137

      Pages: 487-494

    • NAID

      10017344557

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Normal human sera contain bactericidal IgG that binds to the oligosaccharide epitope expressed within lipooligosaccharides of Neisseria gonorrhoeae2005

    • Author(s)
      R.Yamasaki, T.Maruyama, U.Yabe, S.Asuka
    • Journal Title

      Journal of Biochemistry (印刷中)

    • NAID

      10017344557

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Synthesis of a 3,4-di-O-substituted heptose structure : a partial oligosaccharide expressed in Neisserial lipooligosaccharide2004

    • Author(s)
      H.Kubo, K.Ishii, H.Koshino, K.Toubetto, K.Naruchi, R.Yamasaki
    • Journal Title

      Eur.J.Org.Chem.

      Pages: 1202-1214

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Synthesis of a 2,3-di-O-substituted heptose structure by regioselective 3-O-silylation of a 2-O-substituted heptose derivative2004

    • Author(s)
      K.Ishii, Y.Esumi, Y.Iwasaki, R.Yamasaki
    • Journal Title

      Eur.J.Org.Chem.

      Pages: 1214-1227

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Synthesis of a 3,4-di-O-substituted heptose structure : a partial oligosaccharide expressed in Neisseria lipooligosaccharide2004

    • Author(s)
      H.Kubo, K.Ishii, H.Koshino, K.Toubetto, K.Naruchi, R.Yamasaki
    • Journal Title

      Eur.J.Org.Chem.

      Pages: 1202-1213

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 細菌感染と糖鎖2003

    • Author(s)
      山崎 良平
    • Journal Title

      化学と生物 41

      Pages: 15-21

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A novel method for the formation of N-glycoside using hydroxamate2003

    • Author(s)
      J.Nakano, T.Ichiyanagi, H.Ohta, Y.Ito
    • Journal Title

      Tetrahedron Lett 44

      Pages: 2853-2856

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Chemoselective peptide bond Formation using formyl-substituted nitrophenyl-thio ester2003

    • Author(s)
      A.Ishiwata, I.Ichiyanagi, M.Takatani, Y.Ito
    • Journal Title

      Tetrahedron Lett. 44

      Pages: 3187-3190

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Saikin Kannsenn to Tousa2003

    • Author(s)
      Ryohei Yamasaki
    • Journal Title

      Kagaku to Seibutsu 41

      Pages: 15-21

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A novel method for the formation of N-glycoside using hydroxamate2003

    • Author(s)
      Jun Nakano, Tsuyoshi Ichiyanagi, Hiromichi Ohta, Yukishige Ito
    • Journal Title

      Tetrahedron Lett. 44

      Pages: 2853-2856

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Chemoselective Peptide Bond Formation Using Formyl-Substituted Nitrophenylthio Ester2003

    • Author(s)
      A.Ishiwata, T.Ichiyanagi, M.Takatani, Y.Ito
    • Journal Title

      Tetrahedron Lett. 44

      Pages: 3187-3190

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Synthesis of α-lactosyl-(l-3)-L-glycero-α-D-manno-heptopyranoside, a partial oligosaccharide structure expressed within lipooligosaccharide produced by Neisseria gonorrhoeae strain 152532002

    • Author(s)
      K.Ishii, H.Kubo, R.Yamasaki
    • Journal Title

      Carbohydr.Res. 337

      Pages: 11-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mass spectrometric strategy for the characterization of lipooligosaccharides from Neisseria gonorrhoeae 302 using FTICR2002

    • Author(s)
      M.D.Leavell, J.A.Leary, R.Yamasaki
    • Journal Title

      J.Ame.Soc.Mass Spectrometry 13

      Pages: 571-576

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Synthesis of α-lactosyl-(1-3)-L-glycero-α-D-manno-heptopyranoside, a partial oligosaccharide structure expressed within lipooligosaccharide produced by Neisseria gonorrhoeae strain 152532002

    • Author(s)
      K.Ishii, H.Kubo, R.Yamasaki
    • Journal Title

      Carbohydr.Res. 337

      Pages: 11-20

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] K.Ishii, Y.Esumi, Y.Iwasaki, R.Yamasaki: "Synthesis of a 2,3-Di-O-substituted Heptose Structure via Regioselective 3-O-Silviation of a 2-O-Substituted Heptose Derivative"Eur.J.Org.Chem.. 1202-1213 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Kubo, K.Ishii, K.Toubetto, H.Koshino, K.Naruchi, R.Yamasaki: "Synthesis of a 3,4-Di-O-substituted Heptose Structure, a Partical Oligosaccharide Expressed in Neisserial Lipooligosaccharide"Eur.J.Org.Chem.. 1214-1227 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] J.Nakano, T.Ichiyanagi, H.Ohta, Y.Ito: "A Novel Method for the Formation of N-Giycoside Using Hydroxamate"Tetrahedron Lett. 44. 2853-2856 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] B.Ishiwata, T.Ichiyanagi, M.Takatani, Y.Ito: "Chemoselective Peptide Bond Formation Using Formyl-Substituted Nitrophenylthio Ester"Tetrahedron Lett. 44. 3187-3190 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.D.Leavell, J.A.Leary, R.Yamasaki: "Mass spectrometric strategy for the characterization of lipooligosaccharides from Neisseria gononhoeae 302 using FTLCR"J. Ame. Soc. Mass Spectrometiy. 13. 571-576 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Ichiyanagi, M.Takatani, K.Sakamoto, Y.Nakahara, Y.Ito, H.Hojo, Y.Nakahara: "Synthesis of Mucin-Type Glycopeptide (b hCG 130-145) by On-resin Fragment Condensation of the Glycopeptide Segment Carrying Unmasked Oligosaccharides"Tetrahedron Lett. 43. 3297-3300 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Jun Nakano, Tsuyoshi Ichiyanagi, Hiromichi Ohta, Yukishige Ito: "A novel method for the formation of N-lycoside using hydroxarnate"Tetrahedron Lett. 44. 2853-2856 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akihiro Ishiwata, Tsuyoshi Ichiyanagi, Maki Takatani, Yukishige Ito: "Chernoselective Peptide Bond Formation Using Formyl-Substituted Nitrophenylthio Ester"Tetrahedron Lett. 44. 3187-3190 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山崎 良平: "感染と糖鎖"化学と生物. 41・1. 15-21 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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