• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Structure and function of the novel autophagy inducer, (+)-epogymnolactam

Research Project

Project/Area Number 26450135
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bioorganic chemistry
Research InstitutionHokkaido University

Principal Investigator

Ubukata Makoto  北海道大学, 農学研究院, 特任教授 (60168739)

Co-Investigator(Kenkyū-buntansha) 重冨 顕吾  北海道大学, 農学研究院, 講師 (20547202)
三橋 進也  北海道大学, (連合)農学研究科(研究院), 特任講師 (60526672)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsオートファジー / エポジムノラクタム / 全合成 / 構造活性相関 / セルレニン / 構造ー活性相関 / タンデム型不斉エポキシ化
Outline of Final Research Achievements

To determine the structural requirement of (+)-epogymnolactam (1) for its autophagy-inducing activity, we first synthesized 1 in 8 steps. We next synthesized enantiomer of 1 ((-)-Epo), deepoxy derivative (Deepoxy), linear analog (N,N-Dimethyl), cyclic analog (O-Methyl), analog having C6 side chain (C6), analog having C8 side chain (C8). Structure-activity relationship in these compounds, synthetic intermediate (Amide 8), cerulean (Cer), and 1 indicated the importance of (2R,3S)-epoxy group, lactam structure, length of side chain, and presence or absence of double bond for their biological activities.
Cer inhibited autophagy in NIH 3T3 cells, and C6 and C8 analogs induced autophagy, whereas these two analogs inhibited the degradation of p62. These observations suggest that each molecular target for 1, Cer, and C6 or C8 should be different. The present study would contribute to the development of chemotherapeutic agents for the treatment of various incurable diseases.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (17 results)

All 2017 2016 2015 2014

All Journal Article (8 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 8 results,  Open Access: 2 results,  Acknowledgement Compliant: 4 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (1 results)

  • [Journal Article] Growth mechanism of uncultured actinobacterial strain Leucobacter sp. ASN212 by zinc coproporphyrin.2017

    • Author(s)
      R. Takai, K. Shigetomi, Y. Kamagata, and M. Ubukata
    • Journal Title

      Heterocycles

      Volume: 95 Pages: 145-151

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Quercetin inhibits advanced glycation end product formation via chelating metal ions, trapping methylglyoxal, and trapping reactive oxygen species.2017

    • Author(s)
      M.N.I. Buiyan, S. Mitsuhashi, K. Shigetomi, and M. Ubukata
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 81 Pages: 882-890

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Zincmethylphyrins and coproporphyrins, novel growth factors released by Sphingopyxis sp., enable laboratory cultivation of previously uncultured Leucobacter sp. through interspecies mutualism.2016

    • Author(s)
      M.N.I. Bhuiyan, R. Takai, S. Mitsuhashi, K. Shigetomi, Y. Tanaka, Y. Kamagata, and M. Ubukata
    • Journal Title

      The Journal of Antibiotics

      Volume: 69 Pages: 97-103

    • NAID

      120005749616

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Guideline for the use and interpretation of assays for monitoring autophagy (3rd edition)2016

    • Author(s)
      D.J.Klionsky and M. Ubukata et al.
    • Journal Title

      Autophagy

      Volume: 12 Pages: 1-222

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mycophenolic acid and its derivative as potential chemotherapeutic agents targeting inosine monophosphate dehydrogenase in Trypanosoma congolense.2016

    • Author(s)
      K. Suganuma, A.E. Sarwono, S. Mitsuhashi, M. Jxkalski, T. Okada, M. Nthatisi, J. Yamagishi, M. Ubukata, and N. Inoue
    • Journal Title

      Antimicrobial Agents and Chemotherapy

      Volume: 60 Pages: 4391-4393

    • NAID

      120006390948

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] First total synthesis of (+)-epogymnolactam, a novel autophagy inducer2015

    • Author(s)
      Y. Okado, K. Shigetomi, S. Mitsuhashi, and M. Ubukata
    • Journal Title

      The Journal of Antibiotics

      Volume: 68 Pages: 721-724

    • NAID

      120005768785

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] (+)-Epogymnolactam, a novel autophagy iducer from mycerial culture of Gymnopus sp.2015

    • Author(s)
      S. Mitsuhashi, C. Shindo, K. Shigetomi, T. Miyamoto, and M. Ubukata
    • Journal Title

      Phytochemistry

      Volume: 114 Pages: 155-159

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] (+)-Epogymnolactam, a novel autophagy inducer from mycelial culture of Gymnopus sp.2014

    • Author(s)
      S. Mitsuhashi, C. Shindo, K. Shigetomi, T. Miyamoto, and M. Ubukata
    • Journal Title

      Phytochemistry

      Volume: なし Pages: 163-167

    • DOI

      10.1016/j.phytochem.2014.08.012

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 新規オートファジー誘導物質(+)-エポジムノラクタムの構造活性相関2017

    • Author(s)
      岡戸祐治、上田一貴、重冨顕吾、生方 信
    • Organizer
      日本農芸化学会2017年度大会
    • Place of Presentation
      京都女子大(京都府・京都)
    • Year and Date
      2017-03-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 小さな分子から生命が見える2016

    • Author(s)
      生方 信
    • Organizer
      平成28年度 公益社団法人 日本農芸化学会 北海道支部第2回講演会
    • Place of Presentation
      北海道大学(北海道・札幌)
    • Year and Date
      2016-11-23
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] オートファジー誘導物質(+)-Epogymnolactamの類縁体合成および活性評価2016

    • Author(s)
      上田一貴、岡戸祐治、重冨顕吾、生方 信
    • Organizer
      日本木材学会北海道支部・平成28年度研究発表会
    • Place of Presentation
      札幌コンベンションセンター(北海道・札幌)
    • Year and Date
      2016-11-10
    • Related Report
      2016 Annual Research Report
  • [Presentation] 終末糖化産物(AGEs)阻害剤 ー 抽出成分と酸素のインパクト2016

    • Author(s)
      生方 信
    • Organizer
      日本木材学会北海道支部 平成28年度研究発表会
    • Place of Presentation
      札幌コンベンションセンター(北海道・札幌)
    • Year and Date
      2016-11-10
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Lessons from biologically active natural products - Discovery of new growth factors for previously uncultured Leucobacter sp.2016

    • Author(s)
      M. Ubukata
    • Organizer
      BIT's Annual Congress of International Drug discovery Science and Technology -South Korea 2016
    • Place of Presentation
      Korea International Exhibition Center (Gyeonggi, South Korea)
    • Year and Date
      2016-06-29
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] (+)Epogymnolactam の類縁体合成ならびにオートファジー誘導活性評価2016

    • Author(s)
      上田一貴、岡田祐治、重冨顕吾、生方 信
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      札幌コンベンションセンター(北海道・札幌)
    • Year and Date
      2016-03-30
    • Related Report
      2015 Research-status Report
  • [Presentation] (-)-Epogymnolactamの合成研究2015

    • Author(s)
      上田一貴、岡戸祐治、重冨顕吾、生方 信
    • Organizer
      日本木材学会北海道支部・平成27年度(第47回)研究発表会
    • Place of Presentation
      旭川地場産業振興センター(北海道・旭川)
    • Year and Date
      2015-11-13
    • Related Report
      2015 Research-status Report
  • [Presentation] オートファジー誘導物質(+)-Epogymnolactamの単離・構造決定および全合成2014

    • Author(s)
      岡戸祐治、新藤千波耶、重冨顕吾、三橋進也、生方 信
    • Organizer
      日本農芸化学会 北海道支部講演会
    • Place of Presentation
      北海道大学学術交流会館(札幌市)
    • Year and Date
      2014-12-13
    • Related Report
      2014 Research-status Report
  • [Book] 顕著な活性を有する生理活性物質の発見とその化学生物学的展開 平成29年度 日本農学賞受賞論文要旨2017

    • Author(s)
      生方 信
    • Total Pages
      5
    • Publisher
      日本農学会
    • Related Report
      2016 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi