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Analysis of molecular mechanism of anti-asthmatic activity of allosamidin by focusing the function of chitinase-like proteins

Research Project

Project/Area Number 23380062
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bioproduction chemistry/Bioorganic chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

SHOHEI Sakuda  東京大学, 農学生命科学研究科, 准教授 (80192087)

Co-Investigator(Renkei-kenkyūsha) INOUE Hiromasa  鹿児島大学, 大学院・医歯学総合研究科, 教授 (30264039)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2011: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Keywords生物活性物質 / 喘息 / キチナーゼ / キチナーゼ様タンパク質 / アロサミジン / アロサミジンン / デメチルアロサミジン / 抗喘息薬
Research Abstract

Allosamidin, a chitinase inhibitor, shows anti-asthmatic activity toward model mice. Chitinase (AMCase) and chitinase-like proteins (BRP39, Ym1, and Ym2) are possible candidates as target molecules for anti-asthmatic activity of allosamidin. To Recombinant protein of each of the four proteins was prepared and their binding activity toward allosamidin probes, which were newly prepared, was investigated. All the recombinant proteins bound to allosamidin with low Kd values around 10-100 nM. It was found that BRP39 shows protecting activity against death of mouse primary cells. Allosamidin did not inhibit the activity of BRP39 for the cells.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (16 results)

All 2014 2013 2012 2011 Other

All Journal Article (6 results) (of which Peer Reviewed: 3 results) Presentation (10 results) (of which Invited: 2 results)

  • [Journal Article] Thermodynamic analysis of allosamidin binding to the human chitotriosidase2014

    • Author(s)
      Jae Youn Cho, Peter Rosenthal, Maria Miller, Alexa Pham, Seema Aceves, Shohei Sakuda, and David H. Broide
    • Journal Title

      Int. Immunol

      Volume: 565 Pages: 146

    • DOI

      10.1016/j.tca.2013.04.022

    • URL

      https://pure.teikyo.jp/en/publications/00e6f6ed-f242-46fe-a0d7-7d0c070be2bd

    • Related Report
      2013 Final Research Report
  • [Journal Article] Chitinase inhibition promotes atherosclerosis in hyperlipidemic mice2013

    • Author(s)
      Kitamoto S, Egashira K, Ichiki T, Han X, McCurdy S, Sakuda S, Sunagawa K, Boisvert WA.
    • Journal Title

      Am J Pathol.

      Volume: 183 Issue: 1 Pages: 313

    • DOI

      10.1016/j.ajpath.2013.04.003

    • URL

      https://pure.teikyo.jp/en/publications/fcddc203-4bb2-4211-8007-02359b362230

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel biological activities of allosamidins2013

    • Author(s)
      Shohei Sakuda, Hiromasa Inoue, and Hiromichi Nagasawa
    • Journal Title

      Molecules

      Volume: 18 Issue: 6 Pages: 6952

    • DOI

      10.3390/molecules18066952

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Journal Article] Targeting AMCase reduces esophageal eosinophilic inflammation and remodeling in a mouse model of egg induced eosinophilic esophagitis2013

    • Author(s)
      Kristine Bistrup Eide, Silje Thoresen Lundmark, Shohei Sakuda, and Morten Sorlie
    • Journal Title

      Thermochimica Acta

      Volume: 18 Issue: 1 Pages: 35

    • DOI

      10.1016/j.intimp.2013.10.026

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Preparation of allosamidin and demethylallosamidin photoaffinity probes and analysis of allosamidin-binding proteins in asthmatic mice2011

    • Author(s)
      Yosuke Sato, Shigeo Suzuki, Seiko Muraoka, Naoya Kikuchi, Naotaka Noda, Takafumi Matsumoto, Hiromasa Inoue, Hiromichi Nagasawa, and Shohei Sakuda
    • Journal Title

      Bioorg. Med. Chem

      Volume: 19 Issue: 10 Pages: 3054

    • DOI

      10.1016/j.bmc.2011.04.012

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] マウスのキチナーゼおよびキチナーゼ様タンパク質とアロサミジン類2011

    • Author(s)
      村岡聖子
    • Journal Title

      キチンキトサン研究

      Volume: 17 Pages: 70-73

    • Related Report
      2011 Annual Research Report
  • [Presentation] キチナーゼ/キチナーゼ様タンパク質に着目したアロサミジン類の抗喘息作用の解析2014

    • Author(s)
      桑田一平, 井上博雅, 作田庄平, 他4名
    • Organizer
      日本農芸化学会2014年度大会
    • Place of Presentation
      神奈川
    • Year and Date
      2014-03-28
    • Related Report
      2013 Final Research Report
  • [Presentation] Novel biological activities of allosamidins2013

    • Author(s)
      作田庄平
    • Organizer
      10th Asia-Pacific Chitin & Chitosan Synposium
    • Place of Presentation
      米子
    • Year and Date
      2013-10-06
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Studies on the target molecules of allosamidins in their anti-asthmatic activity2013

    • Author(s)
      桑田一平, 井上博雅, 作田庄平, 他5名
    • Organizer
      10th Asia-Pacific Chitin & Chitosan Synposium
    • Place of Presentation
      米子
    • Year and Date
      2013-10-06
    • Related Report
      2013 Final Research Report
  • [Presentation] 抗喘息作用物質アロサミジン類の標的分子の探索2013

    • Author(s)
      桑田一平, 井上博雅, 作田庄平, 他5名
    • Organizer
      日本農芸化学会2013年度大会
    • Place of Presentation
      宮城県
    • Year and Date
      2013-03-26
    • Related Report
      2013 Final Research Report
  • [Presentation] Studies on the target molecules of allosamidins in their anti-asthmatic activity2013

    • Author(s)
      桑田一平、作田庄平他6名
    • Organizer
      10th Asia-Pacific Chitin & Chitosan Symposium
    • Place of Presentation
      Yonago Convention Center(鳥取県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] アロサミジン類とキチナーゼ/キチナーゼ様タンパク質との相互作用解析2012

    • Author(s)
      桑田一平, 井上博雅, 作田庄平, 他3名
    • Organizer
      第26回キチンキトサンシンポジウム
    • Place of Presentation
      北海道
    • Year and Date
      2012-07-12
    • Related Report
      2013 Final Research Report
  • [Presentation] Novel biological activities of allosamidins

    • Author(s)
      作田庄平
    • Organizer
      10th Asia-Pacific Chitin & Chitosan Symposium
    • Place of Presentation
      Yonago Convention Center(鳥取県)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] キチナーゼ/キチナーゼ様タンパク質に着目したアロサミジン類の抗喘息作用の解析

    • Author(s)
      桑田一平、作田庄平他5名
    • Organizer
      日本農芸化学会2014年度大会
    • Place of Presentation
      明治大学生田キャンパス(神奈川県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] アロサミジン類とキチナーゼ/キチナーゼ様タンパク質との相互作用解析

    • Author(s)
      桑田一平、作田庄平他4名
    • Organizer
      第26回キチン・キトサンシンポジウム
    • Place of Presentation
      北海道大学(北海道)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 抗喘息作用物質アロサミジン類の標的分子の探索

    • Author(s)
      桑田一平、作田庄平他6名
    • Organizer
      日本農芸化学会2013年度大会
    • Place of Presentation
      東北大学(宮城県)
    • Related Report
      2012 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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