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Development of antibodies with Abeta hydrolyzing activity for treatment of Alzheimer's disease

Research Project

Project/Area Number 24590151
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Drug development chemistry
Research InstitutionSuzuka University of Medical Science

Principal Investigator

TAGUCHI Hiroaki  鈴鹿医療科学大学, 薬学部, 准教授 (20549068)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords医薬品化学
Outline of Final Research Achievements

Accumulation of amyloid-β-peptide (Aβ) in the brain is one of the pathological hallmarks of Alzheimer’s disease (AD) and has been considered to play a crucial role in the neurodegenerative events underlying AD. Catalytic Abs capable of binding and hydrolyzing Aβ are candidates as immunotherapeutic agents for AD due to their ability to inactivate multiple Aβ molecules per Ab molecule.
In this study, we designed and synthesized phosphonate esters that could be induced production of Abs capable of hydrolytic activity. Evaluation of phosphonate esters containing a hydroxyl group or motif that can capture a water molecule was carried out using trypsin as a model of catalytic Abs. According to the assay results, most promising phosophonate ester to induce catalytic Abs was used for the synthesis of the reagent that can induce Abs capable of binding and hydrolyzing Aβ.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (21 results)

All 2015 2014 2013 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results,  Acknowledgement Compliant: 2 results) Presentation (14 results) (of which Invited: 1 results)

  • [Journal Article] Synthesis of isopeptidyl phosphonate derivatives2015

    • Author(s)
      Taguchi H, Etou D, Oode M, Oohashi S, Ogawa M, and Fujita Y.
    • Journal Title

      Peptides 2014

      Volume: 33

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Specific Amyloid β Clearance by a Catalytic Antibody Construct2015

    • Author(s)
      Planque SA, Nishiyama Y, Sonoda S, Lin Y, Taguchi H, Hara M, Kolodziej S, Mitsuda Y, Gonzalez V, Sait HB, Fukuchi K, Massey RJ, Friedland RP, O'Nuallain B,Sigurdsson EM, Paul S
    • Journal Title

      J Biol Chem.

      Volume: 290 Issue: 16 Pages: 10229-10241

    • DOI

      10.1074/jbc.m115.641738

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and development of peptides directed to drugs2014

    • Author(s)
      Taguchi H
    • Journal Title

      Chemical Industry

      Volume: 65 Pages: 897-902

    • NAID

      40020272329

    • Related Report
      2014 Annual Research Report
    • Acknowledgement Compliant
  • [Journal Article] Metal-dependent amyloid β-degrading catalytic antibody construct2014

    • Author(s)
      Nishiyama Y., Taguchi H., Hara M., Planque S.A., Mitsuda Y., and Paul S
    • Journal Title

      J Biotechnol

      Volume: 180 Pages: 17-22

    • DOI

      10.1016/j.jbiotec.2014.03.026

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis and Biochemical Evaluation of Isopeptidyl Phosphonate Ester Derivatives containing Hydroxyl Group or Macrocyclic Polyamine2014

    • Author(s)
      Taguchi, H., Ogawa, M., Oohashi, S., Fujita, Y.
    • Journal Title

      Peptide Science

      Volume: 50 Pages: 153-154

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Design and synthesis of biotinylated peptidyl phosphonate probe for the isolation of single chain Fv with hydrolyzing activity2013

    • Author(s)
      Hiroaki Taguchi, Yoshio Fujita, Yuko Tsuda
    • Journal Title

      Peptide 2012

      Volume: 32 Pages: 196-197

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Design and Synthesis of Peptidyl Phosphonate for Isolation of Antibodies with Hydrolyzing Activity2013

    • Author(s)
      Hiroaki Taguchi, Yoshio Fujita, Yuko Tsuda
    • Journal Title

      Peptide Science

      Volume: 49 Pages: 301-302

    • NAID

      10031161635

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 部分アミロイドβペプチド配列を含む消光性蛍光基質の開発2015

    • Author(s)
      田口博明,上村尚子,松島慶,藤田快男,
    • Organizer
      第135回日本薬学会
    • Place of Presentation
      兵庫県神戸市
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 抗体医薬開発ツールとしてのリン酸ジエステル含有ペプチドの開発2015

    • Author(s)
      田口博明
    • Organizer
      第20回ペプチドフォーラム「生命分子・ペプチド機能に学ぶ医薬品」
    • Place of Presentation
      滋賀県長浜市
    • Year and Date
      2015-03-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Synthesis of isopeptidyl phosphonate derivatives and their biochemical evaluation2014

    • Author(s)
      Taguchi H, Etou D, Oode M, Oohashi S, Ogawa M, and Fujita Y.
    • Organizer
      33rd European Peptide Symposium
    • Place of Presentation
      ブルガリア,ソフィア
    • Year and Date
      2014-08-31 – 2014-09-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] 加水分解活性を有する抗体の誘導を目指した試薬の開発2014

    • Author(s)
      衛藤大輝,大出慎,佐々木みく,森本佐知子,藤田快男,田口博明
    • Organizer
      第60回日本薬学会東海支部大会
    • Place of Presentation
      三重県鈴鹿市
    • Year and Date
      2014-07-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] 水酸基を有するイソペプチドリン酸ジエステル誘導体の合成と酵素阻害活性評価2014

    • Author(s)
      田口博明,衛藤大輝,大出慎,小川光広,大橋駿,藤田快男
    • Organizer
      第134回日本薬学会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] 水酸基を有するイソペプチドリン酸ジエステル誘導体の酵素阻害活性評価2013

    • Author(s)
      小川光広,大橋駿,藤田快男,田口博明
    • Organizer
      第59回日本薬学会東海支部大会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Research-status Report
  • [Presentation] Synthesis and Biochemical Evaluation of Isopeptidyl Phosphonate Ester Derivatives containing Hydroxyl Group or Macrocyclic Polyamine2013

    • Author(s)
      Taguchi, H., Ogawa, M., Oohashi, S., Fujita, Y.
    • Organizer
      4th Asia-Pacific international Peptide Symposium
    • Place of Presentation
      大阪
    • Related Report
      2013 Research-status Report
  • [Presentation] 環状ポリアミンを含んだイソペプチドリン酸誘導体の合成と酵素阻害活性評価2013

    • Author(s)
      大橋駿,小川光広,藤田快男,田口博明
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会
    • Place of Presentation
      鈴鹿
    • Related Report
      2013 Research-status Report
  • [Presentation] 水酸基を有するイソペプチドリン酸誘導体の合成とそのトリプシン阻害活性2013

    • Author(s)
      小川光広,大橋駿,藤田快男,田口博明
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会
    • Place of Presentation
      鈴鹿
    • Related Report
      2013 Research-status Report
  • [Presentation] アミロイドβペプチド加水分解抗体の単離を指向したプローブの開発

    • Author(s)
      田口博明,藤田快男,津田裕子
    • Organizer
      日本ケミカルバイオロジー学会 第7回年会
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Presentation] 触媒抗体単離を目指したプローブの開発

    • Author(s)
      田口博明,藤田快男,津田裕子
    • Organizer
      第57回日本薬学会東海支部大会
    • Place of Presentation
      静岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Design and synthesis of biotinylated peptidyl phosphonate probe for the isolation of single chain Fv with hydrolyzing activity

    • Author(s)
      Hiroaki Taguchi, Yoshio Fujita, Yuko Tsuda
    • Organizer
      32nd European Peptide Symposium
    • Place of Presentation
      Athens, Greek
    • Related Report
      2012 Research-status Report
  • [Presentation] 加水分解活性を有する抗体の単離を指向したペプチド性リン酸ジエステルのデザインと合成

    • Author(s)
      田口博明,藤田快男,津田裕子
    • Organizer
      第49回ペプチド討論会
    • Place of Presentation
      鹿児島
    • Related Report
      2012 Research-status Report
  • [Presentation] 環状ポリアミンを含んだペプチド性リン酸ジエステル誘導体の合成

    • Author(s)
      田口博明,大橋駿,小川光広,藤田快男
    • Organizer
      第133回日本薬学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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