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Development of anti-HIV agents targeting weak points of viral replication mechanism

Research Project

Project/Area Number 26670053
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Drug development chemistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Tamamura Hirokazu  東京医科歯科大学, 生体材料工学研究所, 教授 (80217182)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords抗HIV薬 / 多量体形成 / カプシドタンパク質 / エンベロープタンパク質gp41 / ペプチドライブラリー / 治療標的 / HIV感染症 / エイズ / 薬剤耐性ウイルス / フォワードケミカルゲノミクス / 抗エイズ薬 / 耐性ウイルス / 部分ペプチドライブラリー / ペプチドミミック
Outline of Final Research Achievements

In this study we tried to develop novel anti-HIV agents based on our new concept. HIV proteins have some structures required for function maintenance involving oligomerization, which might be difficult to mutate. It is important to search these targets in the development of drug seeds. Capsid proteins and an envelope protein gp41 relevant to oligomer formation might have conformationally weak regions against mutation. We tried to search these regions. In consideration of these weal points as our targets, anti-HIV leads were found using peptide libraries. Finally, treatment targets were elucidated and breakthrough for creation of anti-HIV agents was accomplished.

Report

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

    (18 results)

All 2016 2015 2014

All Journal Article (9 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 9 results,  Open Access: 9 results,  Acknowledgement Compliant: 4 results) Presentation (9 results) (of which Int'l Joint Research: 5 results,  Invited: 6 results)

  • [Journal Article] Small-Molecule CD4 Mimics Containing Mono-cyclohexyl Moieties as HIV Entry Inhibitors.2016

    • Author(s)
      Nami Ohashi1, Shigeyoshi Harada, Takaaki Mizuguchi1, Yu Irahara1, Yuko Yamada, Misato Kotani, Wataru Nomura, Shuzo Matsushita, Kazuhisa Yoshimura, Hirokazu Tamamura.
    • Journal Title

      Chem Med Chem

      Volume: 19 Issue: 8 Pages: 940-946

    • DOI

      10.1002/cmdc.201500590

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A minimally cytotoxic CD4 mimic as an HIV entry inhibitor2016

    • Author(s)
      Takaaki Mizuguchi, Shigeyoshi Harada, Tomoyuki Miura, Nami Ohashi, Tetsuo Narumi, Hiromi Mori, Yu Irahara, Yuko Yamada, Wataru Nomura, Shuzo Matsushita, Kazuhisa Yoshimura, Hirokazu Tamamura
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 26 Issue: 2 Pages: 397-400

    • DOI

      10.1016/j.bmcl.2015.11.103

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exploration of Labeling of Near Infrared Dyes on the Polyproline Linker for Bivalent-Type CXCR4 Ligands.2016

    • Author(s)
      Wataru Nomura, Haruo Aikawa, Shohei Taketomi, Miho Tanabe, Takaaki Mizuguchi & Hirokazu Tamamura
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 23 Issue: 21 Pages: 6967-6973

    • DOI

      10.1016/j.bmc.2015.09.040

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Utilization of the Heavy Atom Effect for the Development of a Photosensitive 8-Azacoumarin-Type Photolabile Protecting Group2015

    • Author(s)
      Hikaru Takano, Tetsuo Narumi, Wataru Nomura, Toshiaki Furuta, and Hirokazu Tamamura
    • Journal Title

      Organic Letters

      Volume: 17 Issue: 21 Pages: 5372-5375

    • DOI

      10.1021/acs.orglett.5b02720

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Trivalent Lignds for CXCR4 Bearing Polyproline Linkers Show Specific Recognition for Cells with Increased CXCR4 Expression.2015

    • Author(s)
      Wataru Nomura, Taisuke Koseki, Nami Ohashi, Takaaki Mizuguchi & Hirokazu Tamamura
    • Journal Title

      Org. Biomol. Chem.

      Volume: 13 Issue: 32 Pages: 8734-8739

    • DOI

      10.1039/c5ob00891c

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Anti-HIV Screening for Cell-Penetrating Peptides Using Chloroquine and Identification of Anti-HIV Peptides Derived from Matrix Proteins.2015

    • Author(s)
      Takaaki Mizuguchi, Nami Ohashi, Wataru Nomura, Mao Komoriya, Chie Hashimoto, Naoki Yamamoto, Tsutomu Murakami & Hirokazu Tamamura
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 23 Issue: 15 Pages: 4423-4427

    • DOI

      10.1016/j.bmc.2015.06.020

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] An In-cell Fluorogenic Tag-probe System for Protein Dynamics Imaging Enabled by Cell-Penetrating Peptides.2015

    • Author(s)
      Wataru Nomura, Nami Ohashi, Atsumi Mori & Hirokazu Tamamura
    • Journal Title

      Bioconjugate Chem.

      Volume: 26 Issue: 6 Pages: 1080-1085

    • DOI

      10.1021/acs.bioconjchem.5b00131

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Development of a Traceable Linker Containing a Thiol-responsive Amino Acid for the Enrichment and Selective Labelling of Target Proteins.2014

    • Author(s)
      Yamamoto J, Denda M, Maeda N, Kita M, Komiya C, Tanaka T, Nomura W, Tamamura H, Sato Y, Yamauchi A, Shigenaga A, Otaka A.
    • Journal Title

      Org Biomol Chem

      Volume: 12-23

    • NAID

      120006510952

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Imidazolium Salt-Catalyzed Friedel-Crafts-Type Conjugate Addition of Indoles: Analysis of Indole/Imidazolium Complex by High Level ab Initio Calculations.2014

    • Author(s)
      Narumi T, Tsuzuki S, Tamamura H.
    • Journal Title

      Asian J Org Chem

      Volume: 3-4

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] HIV外被タンパク質gp41由来ペプチドC34の二量体を基盤とした膜融合阻害剤2016

    • Author(s)
      玉村啓和
    • Organizer
      日本薬学会第136年会シンポジウム「抗ウイルス感染症のフロンティア」
    • Place of Presentation
      パシフィコ横浜、神奈川県横浜市
    • Year and Date
      2016-03-28
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Multivalent ligands for CXCR4 with polyproline linkers showing specific recognition for its expression2015

    • Author(s)
      玉村啓和
    • Organizer
      The 7th International Peptide Symposium
    • Place of Presentation
      Singapore, Singapore
    • Year and Date
      2015-12-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Multivalent ligands showing specific recognition for CXCR4 expression2015

    • Author(s)
      玉村啓和
    • Organizer
      The Seventh Peptide Engineering Meeting (PEM7)
    • Place of Presentation
      Pune, India
    • Year and Date
      2015-12-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Peptidomimetic-based Mid-size Drug Research: Anti-HIV Agents2015

    • Author(s)
      玉村啓和
    • Organizer
      The 10th AFMC International Medicinal Chemistry Symposium
    • Place of Presentation
      Jeju, Korea
    • Year and Date
      2015-10-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] An anti-HIV assay method for cell-penetrating peptides using chloroquine and identification of inhibitory peptides derived from matrix proteins2015

    • Author(s)
      玉村啓和
    • Organizer
      The 16th Kumamoto AIDS Seminar
    • Place of Presentation
      阿蘇リゾートグランヴィリオホテル、熊本県阿蘇市
    • Year and Date
      2015-10-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of peptide-lead anti-HIV agents and chemical biology2015

    • Author(s)
      玉村啓和
    • Organizer
      Seminar Series in University of Nebraska Medical Center
    • Place of Presentation
      Omaha, USA
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ペプチドを基盤とした中分子創薬研究-抗HIV剤の創製2015

    • Author(s)
      玉村啓和
    • Organizer
      第21回ペプチドフォーラム
    • Place of Presentation
      東京薬科大学サテライトキャンパス、東京都千代田区
    • Year and Date
      2015-08-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Development of peptide-lead anti-HIV agents.2014

    • Author(s)
      Tamamura H.
    • Organizer
      The 15th Akabori Conference 2014: Japanese-German Symposium on Peptide Science,
    • Place of Presentation
      Boppard, Germany
    • Year and Date
      2014-09-07 – 2014-09-09
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Genome Engineering Cutting-Edge Research and Applications2014

    • Author(s)
      Nomura W, Masuda A, Tamamura H.
    • Organizer
      Enhanced Gene Disruption by Simultaneous Digestion of ZFN or CRISPR/Cas System at hTERT Promoter Region. FASEB SRC
    • Place of Presentation
      Nassau, Bahamas,
    • Year and Date
      2014-06-22 – 2014-06-27
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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