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Elucidation of the reaction process of the pigmentation in alkaptonuria, and development of rapid diagnosis of alkaptonuria

Research Project

Project/Area Number 18K19185
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 38:Agricultural chemistry and related fields
Research InstitutionTokyo University of Science

Principal Investigator

Kuramochi Kouji  東京理科大学, 理工学部応用生物科学科, 教授 (90408708)

Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywordsアルカプトン尿症 / ホモゲンチジン酸 / ベンゾキノン酢酸 / アスコルビン酸 / 重合反応 / 二量化 / 二量化反応 / イオン性液体
Outline of Final Research Achievements

We have studied the oxidative dimerization reaction of homogentisic acid, which is one of the characteristics of alkaptonuria. We examined the dimerization reaction of homogentisic acid and its analogs under various conditions and revealed that the dimerization will proceed via highly reactive benzoquinone acetic acid, an oxidant of homogentisic acid. Furthermore, we established a screening system for identifying compounds, which inhibits the dimerization reaction. These findings can be important clues in the elucidation of the pathological mechanism of alkaptonuria.

Academic Significance and Societal Importance of the Research Achievements

アルカプトン尿症は常染色体劣勢遺伝の代謝疾患で、尿中に多量のホモゲンチジン酸が排出される。また体内に蓄積したホモゲンチジン酸の酸化重合により生成する色素が原因で重篤な関節炎を引き起こすことが知られている。本疾患の予防法・治療法は未だ確立されておらず、従来の診断法も課題が多い。本研究でホモゲンチジン酸の重合阻害剤の探索が可能なスクリーニング系を確立することに成功した。今後、このスクリーニング系は、アルカプトン尿症の治療薬候補の探索に活用されることが期待される。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2020 2019 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Dimerizations of 2-bromo-3-methyl-1,4-naphthoquinone and 2-methyl-1,4-naphthoquinone in tetra-n-butylammonium bromide2020

    • Author(s)
      Onuki Mai、Ota Motohiro、Otokozawa Shoya、Kamo Shogo、Tomoshige Shusuke、Tsubaki Kazunori、Kuramochi Kouji
    • Journal Title

      Tetrahedron

      Volume: 76 Issue: 6 Pages: 130899-130899

    • DOI

      10.1016/j.tet.2019.130899

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthetic and Biological Studies of Juglorubin and Related Naphthoquinones2019

    • Author(s)
      Kamo Shogo、Saito Tatsuo、Kusakabe Yasuha、Tomoshige Shusuke、Uchiyama Masanobu、Tsubaki Kazunori、Kuramochi Kouji
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 84 Issue: 21 Pages: 13957-13966

    • DOI

      10.1021/acs.joc.9b02119

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] 有機合成から生命科学へのアプローチ2020

    • Author(s)
      倉持幸司
    • Organizer
      日本農芸化学会 2020 年度大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] イオン性液体中での 1,4- ナフトキノン類の特異な二量化反応2019

    • Author(s)
      大貫真依,太田元博,男澤翔矢,加茂翔伍,友重秀介,椿一典,倉持幸司
    • Organizer
      第37回 メディシナルケミストリーシンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] イオン性液体中でのキノン二量化反応による有用化合物の効率的合成2018

    • Author(s)
      大貫真依,太田元博,加茂翔伍,友重秀介,椿一典,倉持幸司
    • Organizer
      日本農芸化学会関東支部 2018 年度支部大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Bioinspired Syntheses of Natural Naphthoquinone Dimers2018

    • Author(s)
      Kouji Kuramochi
    • Organizer
      International Congress on Pure & Applied Chemistry Langkawi
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2018-07-25   Modified: 2021-02-19  

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