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Design and synthesis of anti-HIV agents that inhibit the Vif-mediated proteasome degradation of APOBEC3G

Research Project

Project/Area Number 22659024
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Drug development chemistry
Research InstitutionKumamoto University

Principal Investigator

OTSUKA Masami  熊本大学, 大学院・生命科学研究部, 教授 (40126008)

Co-Investigator(Kenkyū-buntansha) FUJITA Mikako  熊本大学, 薬学部附属創薬研究センター, 准教授 (00322256)
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥2,960,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywords抗エイズ薬 / Vif / APOBEC3G / HIV-1 / プロテアソーム分解 / NF-κB
Research Abstract

APOBEC3G is a human antiviral protein that blocks HIV-1 replication. However, the antiviral activity of A3G is overcome by the HIV-1 protein Vif that degrades APOBEC3G. We designed and synthesized artificial compounds MF1, MF2, and MF3 to examine the Vif-inhibitory activity. We found that MF2 and MF1(generated by adding DTT to MF2) increase the expression of APOBEC3G to a level much higher than that observed in the absence of Vif, without affecting the level of Vif expression. Furthermore, MF2, MF3, and MF1(generated by adding DTT to MF2 or MF3) significantly inhibited the MAGI cell infectivity of wild-type HIV-1. These findings may contribute to the development of a novel anti-HIV-1 drug.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (23 results)

All 2011 2010 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (10 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] An Artificial Copper Complex Incorporating a Cell-penetrating Peptide Inhibits NF-B Activation2011

    • Author(s)
      Yosuke Kanemaru, Yumi Momiki, Saori Matsuura, Tatsufumi Horikawa, Jin Gohda, Jun-ichiro Inoue, Yoshinari Okamoto, Mikako Fujita, Masami Otsuka
    • Journal Title

      Chem. Pharm. Bull.

      Volume: 59 Pages: 1555-1558

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Design and synthesis of biotinylated inositol 1, 3, 4, 5-tetrakisphosphate targeting Grp1 Pleckstrin Homogy domain2011

    • Author(s)
      Kensaku Anraku, Teruhiko Inoue, Kenji Sugimoto, Kota Kudo, Yoshinari Okamoto, Takashi Morii, Yasuo Mori, Masami Otsuka
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 19 Pages: 6833-6841

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] An anti-HIV-1 compound that increase steady-state expression of apoplipoprotein B mRNA-editing Enzyme-catalytic polypep-tide-like 3G2011

    • Author(s)
      Tomohiko Ejima, Mayuko Hirota, Tamio Mizukami, Masami Otsuka, Mikako Fujita
    • Journal Title

      Int. J. Mol. Med.

      Volume: 28 Pages: 613-616

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] An anti-HIV-1 compound that increase steady-state expression of apoplipoprotein B mRNA-editing Enzyme-catalytic polypeptide-like 3G2011

    • Author(s)
      江島智彦
    • Journal Title

      Int.J.Mol.Med.

      Volume: 28 Pages: 613-616

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An Artificial Copper Complex Incorporating a Cell-penetrating Peptide Inhibits NF-κB Activation2011

    • Author(s)
      金丸陽亮
    • Journal Title

      Chem.Pharm.Bull.

      Volume: 59 Pages: 1555-1558

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design and synthesis of biotinylated inositol 1,3,4,5-tetrakisphosphate targeting Grpl Pleckstrin Homogy domain2011

    • Author(s)
      安楽健作
    • Journal Title

      Bioorg.Med.Chem.

      Volume: 19 Pages: 6833-6841

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Highly Sensitive Analysis of the Interaction between HIV-1 Gag and Phosphoinositide Derivatives Based on Surface Plasmon Resonance2010

    • Author(s)
      Kensaku Anraku, Ryota Fukuda, Nobutoki Takamune, Shogo Misumi, Yoshinari Okamoto, Masami Otsuka, Mikako Fujita
    • Journal Title

      Biochemistry

      Volume: 49 Pages: 5109-5116

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Multifaceted activity of HIV Vpr/Vpx proteins : the current view of their virological functions2010

    • Author(s)
      Mikako Fujita, Masami Otsuka, Masako Nomaguchi, Akio Adachi
    • Journal Title

      Reviews in Medical Virology

      Volume: 20 Pages: 68-76

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Multifaceted activity of HIV Vpr/Vpx proteins : the current view of their virological functions.2010

    • Author(s)
      藤田美歌子
    • Journal Title

      Rev.Med.Virol.

      Volume: 20 Pages: 68-76

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Site-directed mutagenesis of HIV-1 vpu gene demonstrates two clusters of replication-defective mutants with distinct ability to down-regulace cell surface CD4 abd tetherin.2010

    • Author(s)
      野間口雅子
    • Journal Title

      Fmnt.Microbiol.

      Volume: 1 Pages: 116-116

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Highly sensitive analysls of the interaction between HIV-1 Gag and phos phoinositide derivatives based on surface plasmon resonance.2010

    • Author(s)
      安楽健作
    • Journal Title

      Biochemistry

      Volume: 49 Pages: 5109-5116

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 新規チオール化合物の合成と機能解析2011

    • Author(s)
      肥田知浩、金丸陽亮、岡本良成、藤田美歌子、大塚雅巳
    • Organizer
      第28回日本薬学会九州支部大会
    • Place of Presentation
      福岡大学薬学部(福岡)
    • Year and Date
      2011-12-10
    • Related Report
      2011 Final Research Report
  • [Presentation] 新規チオール化合物の合成と機能解析2011

    • Author(s)
      肥田知浩
    • Organizer
      第28回日本薬学会九州支部大会
    • Place of Presentation
      福岡大学(福岡県)
    • Year and Date
      2011-12-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] Systematic Synthesis of all Regioisomers of Inositol Phosphates2011

    • Author(s)
      Takeshi Masuda, Kensaku Anraku, Kaori Sato, Yoshinari Okamoto, Masami Otsuka
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      2011-12-01
    • Related Report
      2011 Final Research Report
  • [Presentation] Design and Synthesis of Anti-HIV-1 Agent that Targets Pr55Gag Protein2011

    • Author(s)
      Kensaku Anraku, Mikako Fujita, Masami Otsuka
    • Organizer
      8^<th> AFMC International Medicinal Chemistry Symposium
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      2011-11-30
    • Related Report
      2011 Final Research Report
  • [Presentation] 酸性脂質類によるHIV-1増殖の抑制2011

    • Author(s)
      安楽健作、藤田美歌子、大塚雅巳
    • Organizer
      第25回日本エイズ学会学術集会
    • Place of Presentation
      ハイアットリージェンシー東京(東京)
    • Year and Date
      2011-11-30
    • Related Report
      2011 Final Research Report
  • [Presentation] PHドメイン分子によるHIV-1放出の制御2011

    • Author(s)
      藤田美歌子、安楽健作、大塚雅巳
    • Organizer
      第25回日本エイズ学会学術集会
    • Place of Presentation
      ハイアットリージェンシー東京(東京)
    • Year and Date
      2011-11-30
    • Related Report
      2011 Final Research Report
  • [Presentation] Systematic synthesis of all regioisomers of inositol phosphates2010

    • Author(s)
      Takashi Masuda, Kensaku Anraku, Kaori Sato, Yoshinari Okamoto, Masami Otsuka
    • Place of Presentation
      PACIFICHEM 2010、Convention Center,(Honolulu)
    • Year and Date
      2010-12-19
    • Related Report
      2011 Final Research Report
  • [Presentation] Pr55^<Gag>を標的とした抗HIV-1薬開発のための基礎的研究2010

    • Author(s)
      安楽健作、福田亮太、藤田美歌子、大塚雅巳
    • Organizer
      第29回メディシナルケミストリーシンポジウム
    • Place of Presentation
      京都テルサ(京都)
    • Year and Date
      2010-11-18
    • Related Report
      2011 Final Research Report
  • [Presentation] HIV-1 MA蛋白質と強く結合する低分子化合物の探索2010

    • Author(s)
      安楽健作、福田亮太、大塚雅巳、藤田美歌子
    • Organizer
      第58回日本ウイルス学会学術集会
    • Place of Presentation
      徳島あわぎんホール(徳島)
    • Year and Date
      2010-11-08
    • Related Report
      2011 Final Research Report
  • [Presentation] HIV Vpr/Vpx蛋白質の役割2010

    • Author(s)
      藤田美歌子
    • Organizer
      第58回日本ウイルス学会学術集会
    • Place of Presentation
      あわぎんホール(徳島県)(招待講演)
    • Year and Date
      2010-11-08
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.pharm.kumamoto-u.ac.jp/Labs/bunsigouseiHP/index.html

    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] APOBEC3発現向上剤及び抗HIV剤2010

    • Inventor(s)
      藤田美歌子、大塚雅巳、江島智彦
    • Industrial Property Rights Holder
      熊本大学
    • Filing Date
      2010-04-28
    • Related Report
      2011 Final Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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