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Attempted synthesis of taxol utilizing anti-taxol monoclonal antibody as a as a chiral mould

Research Project

Project/Area Number 19550114
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Synthetic chemistry
Research InstitutionKansai University

Principal Investigator

UESATO Shinichi  Kansai University, 化学生命工学部, 教授 (50111969)

Co-Investigator(Kenkyū-buntansha) 長岡 康夫  関西大学, 化学生命工学部, 准教授 (90243039)
河野 武幸  摂南大学, 薬学部, 教授 (50178224)
Co-Investigator(Renkei-kenkyūsha) NAGAOKA Yasuo  関西大学, 化学生命工学部, 教授 (90243039)
KOUNO Takeyuki  摂南大学, 薬学部, 教授 (50178224)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords分子認識 / モノクローナル抗体 / タキソール / ハプテン / 抗タキソールモノクローナル抗体 / ハイブリドーマ / 抗体反応 / ニュートラルロスキャン / MS / MS法 / ニュートラルロススキャン / ニュートラルスキャン
Research Abstract

2'-Succinyltaxol-BSA and 2'-succinyltaxol-RSA conjugates were prepared. Formation of a linkage between hapten and protein is usually confirmed by the UV or fluorescamine method. However, it was difficult to confirm the binding of 2'-succinyltaxol to the protein by these methods owing to the similar UV absorption maxima of 2'-succinyltaxol and protein. We therefore conducted a mass spectrometric analysis using the neutral loss scan and MS/MS techniques to confirm the formulation of the 2'-succinyltaxol-protein conjugate. Balb/c mice were immunized i.c. at 2-week intervals each with 2'-Succinyltaxol-RSA. The spleen cells from the mice were treated in a conventional way, giving four hybridomas producing an anti-taxol monoclonal antibody. However, the hybridomas did not have a high production ability of an anti-taxol monoclonal antibody, and their antibody titers were rather low. Unfortunately, production of the antibody declined gradually with cloning. This problem was not improved in spite of our efforts with amounts of antibody and kinds of adjuvant as well as culturing conditions. Condensation reaction between baccacin III and an activated ester (viniyl ester) of C13-carboxylic acid was attempted under a crude antibody as a preliminary experiment. Further examination of the antibody reaction has not yet been conducted owing to a loss of antibody production function.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (12 results)

All 2009 2008 Other

All Journal Article (4 results) (of which Peer Reviewed: 2 results) Presentation (6 results) Remarks (2 results)

  • [Journal Article] Histone deacetylase inhibitor prodrugs in nanoparticle vector enhancedgene expression in human cancer cells.2009

    • Author(s)
      Ishii Y., Hattori Y., Yamada T., Uesato S, Maitani K., Nagaoka Y
    • Journal Title

      Eur. J. Med. Chem 44

      Pages: 4603-4610

    • Related Report
      2009 Final Research Report
  • [Journal Article] Histone deacetylase inhibitor prodrugs in nanoparticle vector enhanced gene expression in human cancer cells2009

    • Author(s)
      Y.Ishii, Y.Hattori, T.Yamada, S.Uesato, Y.Maitani, Y.Nagaoka
    • Journal Title

      Eur.J.Med.Chem. 44

      Pages: 4603-4610

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Attempt to Detect Natural Anticancer Compounds-Protein Binding through Precursor Ion Scan and MS/MS Measurements2008

    • Author(s)
      Negishi J., Shirahama T., Nagaoka Y., Takemoto Y., Uesato S
    • Journal Title

      The Pharmaceutical Society of Japan 128

      Pages: 1317-1323

    • NAID

      110006873990

    • Related Report
      2009 Final Research Report
  • [Journal Article] Attempt to Detect Natural Anticancer Compounds - Protein Binding through Precursor Ion Scan and MS/MS Measurements.2008

    • Author(s)
      J. Negishi, T. Shirahama, Y. Nagaoka, Y. Takemoto, S. Uesato.
    • Journal Title

      J. Pharm. Soc. Japan 128

      Pages: 1317-1323

    • NAID

      110006873990

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 新規細胞周期M期制御化合物の抗がん活性と関連化合物の構造活性相関について2009

    • Author(s)
      瓦谷泰之, 平田佳之, 長岡康夫, 原田知彦, 上里新一, 芝野真喜雄, 谷口雅彦, 安田正秀, 馬場きみ江
    • Organizer
      第28回メディシナルケミストリーシンポジウム
    • Place of Presentation
      東大本郷
    • Year and Date
      2009-11-25
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] Novel M-phase regulating compounds comprising a nitrooxymethyl group in the molecule2009

    • Author(s)
      Uesato S., Kawaratani Y., Nagaoka Y
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-10-03
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] モノクローナル抗体を反応場としたタキソール合成の試み-抗タキソールモノクローナル抗体の作製2009

    • Author(s)
      武本佳樹, 白浜辰弥, 河野武幸, 辻琢己, 盛實祐希, 長岡康夫, 上里新一
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Year and Date
      2009-03-27
    • Related Report
      2009 Final Research Report
  • [Presentation] モノクローナル抗体を反応場としたタキソール合成の試み-抗クキソールモノクローナル抗体の作製2009

    • Author(s)
      武本佳樹, 白浜辰弥, 河野武幸, 辻琢己, 盛實祐希, 長岡康夫, 上里新一
    • Organizer
      日本薬学会129年会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2009-03-27
    • Related Report
      2008 Annual Research Report
  • [Presentation] ニュートラルロスキャン法およびMS/MS法を用いたタキソールータンパク質複合体形成の確認について2009

    • Author(s)
      白浜辰弥, 武本佳樹, 山本智加, 根岸淳, 長岡康夫, 上里新一
    • Organizer
      日本薬学会129年会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2009-03-26
    • Related Report
      2008 Annual Research Report
  • [Presentation] ニュートラルロススキャン法およびMS/MS法を用いたタキソール-タンパク質複合体形成の確認について2009

    • Author(s)
      白浜辰弥, 武本佳樹, 山本智加, 根岸淳, 長岡康夫, 上里新一
    • Organizer
      日本薬学会第129年会
    • URL

      http://pharm.life-bio.kansai-u.ac.jp

    • Place of Presentation
      京都
    • Related Report
      2009 Final Research Report
  • [Remarks]

    • URL

      http://pharm.life-bio.kansai-u.ac.jp

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://pharm.life-bio.kansai-u.ac.jp

    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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