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Design and synthesis of new cationic metal complexes for anticancer drugs and identification of their target molecules

Research Project

Project/Area Number 16K18851
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Chemical pharmacy
Research InstitutionNagoya City University

Principal Investigator

Hisamatsu Yosuke  名古屋市立大学, 大学院薬学研究科, 講師 (80587270)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsがん治療薬 / イリジウム錯体 / カチオン性ペプチド / 細胞死 / ペプチド / 金属錯体 / イリジウム / フォトアフィニティーラベリング / ジアジリン / カルモジュリン / 標的分子
Outline of Final Research Achievements

In this work, we have continued the mechanistic studies of cell death induced by amphiphilic Ir complexes containing cationic peptides. We designed and synthesized new cationic amphiphilic Ir complexes having photoreactive diazirine groups for photoaffinity labeling to identify the target molecules of the Ir complex. A proteomic analysis of the products obtained by the photoirradiation of Ir complex with Jurkat cells suggests that the Ca2+-binding protein “calmodulin (CaM)” is one of target proteins of the Ir complexes. Indeed, cationic amphiphilic Ir complex forms a stable complex with the Ca2+-CaM complex, as evidenced by luminescence titration experiments.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (23 results)

All 2018 2017 2016

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (17 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Stereospecific Synthesis of Tris-heteroleptic Tris-cyclometalated Iridium(III) Complexes via Different Heteroleptic Halogen-Bridged Iridium(III) Dimers and Their Photophysical Properties2018

    • Author(s)
      Yuichi Tamura, Yosuke Hisamatsu, Ayami Kazama, Kenji Yoza, Kyouhei, Sato, Reiko Kuroda, Shin Aok
    • Journal Title

      Inorganic Chemistry

      Volume: 57 Issue: 8 Pages: 4571-4589

    • DOI

      10.1021/acs.inorgchem.8b00323

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design, Synthesis and Anticancer Activity of Cyclometalated Tris(ppy) Iridium (III) Complexes Having the Cationic Peptides at the 4’-Position of Ppy Ligand (ppy = 2-phenylpyridine)2017

    • Author(s)
      Kenta Yokoi, Yosuke Hismaatsu and Shin Aoki
    • Journal Title

      European Journal of Inorganic Chemistry

      Volume: (44) Issue: 44 Pages: 5295-5309

    • DOI

      10.1002/ejic.201700846

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Design and Synthesis of Luminescent Ir Complex-Peptide Hybrids for Theranostics of Cancer2017

    • Author(s)
      Shin Aoki, Yosuke Hisamatsu
    • Journal Title

      Annals of Pharmacology and Pharmaceutics

      Volume: 2 Pages: 1118-1118

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cationic Amphiphilic Tris-Cyclometalated Iridium(III) Complexes Induce Cancer Cell Death via Interaction with Ca2+-Calmodulin Complex.2017

    • Author(s)
      Hisamatsu Y, Suzuki N, Masum AA, Shibuya A, Abe R, Sato A, Tanuma SI, Aoki S.
    • Journal Title

      Bioconjug Chem

      Volume: 28(2) Issue: 2 Pages: 507-523

    • DOI

      10.1021/acs.bioconjchem.6b00627

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Design and Synthesis of Tris-Heteroleptic Cyclometalated Iridium(III) Complexes Consisting of Three Different Nonsymmetric Ligands Based on Ligand-Selective Electrophilic Reactions via Interligand HOMO Hopping Phenomena2017

    • Author(s)
      Yosuke Hisamatsu, Sarvendra Kumar, Shin Aoki
    • Journal Title

      Inorganic Chemistry

      Volume: 56 Issue: 2 Pages: 886-899

    • DOI

      10.1021/acs.inorgchem.6b02519

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Efficient Synthesis of Tris-Heteroleptic Iridium(III) Complexes Based on the Zn2+-Promoted Degradation of Tris-Cyclometalated Iridium (III) Complexes and Their Photophysical Properties2017

    • Author(s)
      Yuichi Tamura, Yosuke Hisamatsu, Sarvendra Kumar, Taiki Itoh, Kyouhei Sato, Reiko Kuroda, Shin Aoki
    • Journal Title

      Inorganic Chemistry

      Volume: 56 Issue: 2 Pages: 812-833

    • DOI

      10.1021/acs.inorgchem.6b02270

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] プロトポルフィリン IX およびその鉄(III)錯体を認識するピンセット型ホスト分子の設計・合成と応用2018

    • Author(s)
      久松洋介、梅澤直樹、樋口恒彦
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Design and Synthesis of Artificial TRAIL Mimics Based on C3-symmetric and Luminescent Iridium Complexes that are Able to Stain and Induce Cell Death of Cancer Cells2017

    • Author(s)
      Abdullah-Al Masum, Yosuke Hisamasu, Nozomi Suzuki, Shin Aoki
    • Organizer
      第15回次世代を担う有機化学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] シクロメタレート型イリジウム錯体-ペプチドハイブリッド化合物によるがん細胞の検出と細胞死誘導―ペプチド配列とペプチド導入位置の影響の検討―2017

    • Author(s)
      青木伸、久松洋介、Abdullah-Al Masum、内藤佳奈、横井 健汰、鈴木 希美
    • Organizer
      日本ケミカルバイオロジー学会第12回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Phenylpyridineリガンド部の4’位にカチオン性ペプチドハイブリッドを導入したシクロメタレート型Ir(III)錯体の設計、合成とがん細胞死誘導活性2017

    • Author(s)
      横井健汰、内藤佳奈、久松洋介、青木伸
    • Organizer
      第27回金属の関与する生体関連反応シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] シクロメタレート型Ir(III)錯体-ペプチドハイブリッドのがん細胞死誘導活性に及ぼすペプチド配列の影響2017

    • Author(s)
      内藤佳奈 、 久松 洋介、 Abdullah-Al Masum、 青木伸
    • Organizer
      第27回金属の関与する生体関連反応シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Selective Cell Death Induction of Cancer Cells of Metal Complexes2017

    • Author(s)
      Jun Jie Zhu, Yosuke Hisamatsu, Shin Aoki
    • Organizer
      6th Asian Conference on Coordination Chemistry
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Detection and Induction of Cell Death of Cancer Cells by Luminescent Iridium Complexes Having Death Receptor Binding Peptides2017

    • Author(s)
      Abdullah-Al Masum, Yosuke Hisamatsu, Nozomi Suzuki, and Shin Aoki
    • Organizer
      17th Asian Chemical Congress (17ACC)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Detection and Cell Death Induction of Cancer Cells by Cyclometalated Ir Complex-Peptide Hybrids (シクロメタレート型イリジウム錯体-ペプチドハイブリッドによるがん細胞の検出と細胞死誘導)2017

    • Author(s)
      青木伸、Abdullah-Al Masum、久松洋介、内藤佳奈、横井健汰
    • Organizer
      2017年光化学討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] へミン認識能を有する分子ピンセットの開発2017

    • Author(s)
      久松洋介、梅澤直樹、樋口恒彦
    • Organizer
      第11回バイオ関連化学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Effect of Peptide Sequences on Cancer Cell Death Induced by Amphiphilic Cyclometalated Iridium(III) Complex-Peptide Hybrids2017

    • Author(s)
      Kana Naito, Yosuke Hisamatsu, Kenta Yokoi, Abdullah-Al Masum, Shin Aoki
    • Organizer
      錯体化学会第67回討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] へミンを認識するピンセット型ホスト分子の設計・合成と生物活性評価2017

    • Author(s)
      久松洋介、梅澤直樹、樋口恒彦
    • Organizer
      第35回メディシナルケミストリーシンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] りん光を消光する官能基を有するシクロメタレート型イリジウム錯体の設計・合成と応用2017

    • Author(s)
      田村祐一、久松洋介、内藤佳奈、横井健汰、青木伸
    • Organizer
      第43回反応と合成の進歩シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Mechanistic Study of Cancer Cell Death Induced by Cationic Amphiphilic Tris-Cyclometalated Iridium (III) Complex and Its Interaction with Target Protein2016

    • Author(s)
      Yosuke Hisamatsu, Nozomi Suzuki, Abdullah-Al Masum, Ai Shibuya, and Shin Aoki
    • Organizer
      8th Asian Biological Inorganic Chemistry Conference
    • Place of Presentation
      オークランド、ニュージーランド
    • Year and Date
      2016-12-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Novel Synthetic Approaches to Cyclometalated Iridium(III) Complexes Having Three Different Ligands2016

    • Author(s)
      Yosuke Hisamatsu, Yuichi Tamura, Sarvendra Kumar, Taiki Itoh, Kyouhei Sato, Reiko Kuroda, Miho Hatanaka, Shin Aoki
    • Organizer
      錯体化学会第66回討論会
    • Place of Presentation
      福岡大学
    • Year and Date
      2016-09-10
    • Related Report
      2016 Research-status Report
  • [Presentation] カチオン性両親媒性イリジウム(III)錯体の細胞死誘導とフォトアフィニティーラベリングを用いた分子機構の解析2016

    • Author(s)
      久松 洋介、鈴木 希美、渋谷 愛、マスム アブドラアル、佐藤 聡、田沼 靖一、青木 伸
    • Organizer
      第10回バイオ関連化学シンポジウム
    • Place of Presentation
      石川県立音楽堂
    • Year and Date
      2016-09-07
    • Related Report
      2016 Research-status Report
  • [Presentation] 細胞死誘導の時間スケールが異なるペプチドを導入した発光性イリジウム錯体の設計・合成と作用メカニズム解析2016

    • Author(s)
      久松 洋介、鈴木 希美、渋谷 愛、マスム アブドラル、 鈴木 利宙、安部 良、青木 伸
    • Organizer
      日本ケミカルバイオロジー学会第11回年会
    • Place of Presentation
      京都テルサ
    • Year and Date
      2016-06-15
    • Related Report
      2016 Research-status Report
  • [Presentation] 機能性イリジウム錯体の精密な設計・合成と生物学的応用2016

    • Author(s)
      久松 洋介、青木 伸
    • Organizer
      第2回材料相模セミナー
    • Place of Presentation
      相模中央化学研究所
    • Related Report
      2016 Research-status Report
    • Invited

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Published: 2016-04-21   Modified: 2019-03-29  

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