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Functional Group Non-selective Carbene Insertion Reaction as a Tool for Chemical Genetic Research

Research Project

Project/Area Number 17510187
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Living organism molecular science
Research InstitutionTohoku University (2006)
The Institute of Physical and Chemical Research (2005)

Principal Investigator

KANOH Naoki  Tohoku University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院薬学研究科, 助教授 (40317293)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsSmall-molecule microarrays / Functioinal-group-independent immobilization / Photo-cross-linkin / Small-molecule affinity matrix / Reactivity of photo-generated carbene species
Research Abstract

1. Photo-Cross-Linked Small-Molecule Microarrays
During the first half of the term of project, the head investigator has optimized the photo-cross-linked small-molecule microarray platform; namely, he prepared and evaluated a variety of linkers connecting a small molecule and a glass slide, and found that a polyethylene glycol linker introduced on the glass slide via a urea linkage was optimal so far. In the latter half of the research period, he screened small-molecule ligands for a variety of proteins by using the optimized platform.
2. Evaluation of the Ractivity of Photo-Generated Aryltrifluoromethyl Carbene Species toward O-H and C-H Bonds within a Molecule
The head investigator has confirmed that (1) the photo-generated aryltrifluoromethyl carbene species was able to insert into not only an O-H bond but also unactivated C-H bonds within a low-molecular weight alcohol at the liquid state, and (2) the ratio of the C-H insertion products dramatically increased when the reaction was performed at the solid state. Furthermore, the structure of all the C-H and O-H insertion products was elucidated by using LC-MS/MS and LC-MS/MS/MS analyses.
3. Photo-Cross-Linked Small-Molecule Affinity Matrix
The head investigator has prepared both conventional-and photo-cross-linked small-molecule affinity matrices, and compared the amount of binding proteins bound to these affinity matrices. As a result, it was demonstrated that the photo-cross-linked small-molecule affinity matrix had the almost same capacity of recovering their binding protein with the conventional small-molecule affinity matrix in some cases.
Then, by using some biologically active small molecules that were stable under an amount of UV irradiation of 365 nm, he
prepared photo-cross-linked small-molecule affinity matrices, and obtained some previously-unknown targets for each small
molecule.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (31 results)

All 2007 2006 2005 Other

All Journal Article (27 results) Book (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Chapter 6. Small-molecule microarrays2007

    • Author(s)
      Naoki Kanoh
    • Journal Title

      Facts in Nanobio probing technology (Ed. by H. Mihara, E. Kobtake, and Y. Baba) Kodansya Scientific, Tokyo (in print)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Detection of small-molecule : protein interactions by using small-moelcule microarrays2007

    • Author(s)
      Akiko Saito
    • Journal Title

      Handbook on the analysis of bimolecular interaction (Ed. by T. Isobe, K. Nakayama, and R. Ito), Yodosya, Japan (in print)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] ナノバイオ計測の実際(第6章 小分子チップ)2007

    • Author(s)
      三原 久和
    • Journal Title

      講談社サイエンティフィク 印刷

    • Related Report
      2006 Annual Research Report
  • [Journal Article] SPR imaging of photo-cross-linked small-molecule microarrays on gold2006

    • Author(s)
      Naoki KANOH
    • Journal Title

      Analytical Chemistry 78

      Pages: 2226-2230

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Reveromycin A, a novel agent for osteoporosis inhibits bone resorption by inducing apoptosis specifically in activated osteoclasts2006

    • Author(s)
      Je-Tae WOO
    • Journal Title

      Proceedings of the National Academy of Science of the United States of America 103

      Pages: 4729-4734

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Photo-cross-linked small-molecule microarrays as chemical genomic tools for dissecting protein-ligand interactions2006

    • Author(s)
      Naoki KANOH
    • Journal Title

      Chemistry-An Asian Journal 1

      Pages: 789-797

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] ケミカルゲノミクス研究用ツールとしての低分子有機化合物のマイクロアレイ化技術2006

    • Author(s)
      叶 直樹
    • Journal Title

      有機合成化学協会誌 64

      Pages: 639-650

    • NAID

      10019174253

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] SPR imaging of photo-cross-linked small-molecule microarrays on gold2006

    • Author(s)
      Naoki Kanoh
    • Journal Title

      Analytical Chemistry 78

      Pages: 2226-2230

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] a novel agent for osteoporosis, inhibits bone resorption by inducing apoptosis specifically in activated osteoclasts2006

    • Author(s)
      Je-Tae Woo, Reveromycin A
    • Journal Title

      Proceedings of the National Academy of Science of the United States of America 103

      Pages: 4729-4734

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Photo-cross-linked small-molecule microarrays as chemical genomic tools for dissecting protein-ligand interactions2006

    • Author(s)
      Naoki Kanoh
    • Journal Title

      Chemistry-An Asian Journal 1

      Pages: 789-797

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Small-molecule microarrays as tools for facilitating chemical genomics : Recent advances2006

    • Author(s)
      Naoki Kanoh
    • Journal Title

      Journal of Synthetic Organic Chemistry, Japan 64

      Pages: 639-650

    • NAID

      10019174253

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Photo-cross-linked small-molecule microarrays as chemical genomic tools for dissecting protein-ligand interactions2006

    • Author(s)
      Naoki KANOH
    • Journal Title

      Chemistry - An Asian Journal 1

      Pages: 789-797

    • Related Report
      2006 Annual Research Report
  • [Journal Article] SPR imaging of photo-cross-linked small-molecule microarrays2006

    • Author(s)
      Naoki KANOH
    • Journal Title

      Analytical Chemistry 78(印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Reveromycin A, a novel agent for osteoporosis inhibits bone resorption by inducing apoptosis specifically in activated osteoclasts2006

    • Author(s)
      Je-Tae WOO
    • Journal Title

      Proceedings of the National Academy of Science of the United States of America 103(発表予定)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] ケミカルゲノミクス研究用ツールとしての低分子有機化合物のマイクロアレイ化技術2006

    • Author(s)
      叶 直樹
    • Journal Title

      有機合成化学協会誌 64(掲載予定)

    • NAID

      10019174253

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Photo-cross-linked small-molecule affinity matrix for facilitating forward and reverse chemical genetics2005

    • Author(s)
      Naoki KANOH
    • Journal Title

      Angewandte Chemie International Edition 44

      Pages: 3559-3562

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Phoslactomycin targets cysteine-269 of protein phosphatase 2A catalytic subunit2005

    • Author(s)
      Takayuki TERUYA
    • Journal Title

      FEBS letters 579

      Pages: 2463-2468

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] バイオプローブの探索と細胞内標的分子の同定2005

    • Author(s)
      臼井 健郎
    • Journal Title

      実験医学 23

      Pages: 1803-1809

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] 天然由来のバイオプローブを用いたケミカルジェネティクスとケミカルゲノミクス2005

    • Author(s)
      叶 直樹
    • Journal Title

      蛋白質核酸酵素 50

      Pages: 1037-1042

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] 化合物マイクロアレイ2005

    • Author(s)
      長田 裕之
    • Journal Title

      バイオテクノロジージャーナル 5

      Pages: 724-727

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Photo-cross-linked small-molecule affinity matrix for facilitating forward and reverse chemical genetics2005

    • Author(s)
      Naoki Kanoh
    • Journal Title

      Angewandte Chemie International Edition 44

      Pages: 3559-3562

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] phoslactomycin targets cycteine-269 of protein phisphatase 2A catalytic subunit2005

    • Author(s)
      Takayuki Teruya
    • Journal Title

      FEBS Letters 579

      Pages: 2463-2468

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Bioprobes in forward and reverse chemical genetics2005

    • Author(s)
      Takeo Usui
    • Journal Title

      Experimental Medicine (Zikken Igaku) 23

      Pages: 1803-1809

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Forward and reverse chemical genetics utilizing naturally occurring bioprobes2005

    • Author(s)
      Naoki Kanoh
    • Journal Title

      Protein, Nucleic Acid and Enzyme (Tanpakusitu Kakusan Kouso) 50

      Pages: 1037-1042

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Small-molecule microarrays2005

    • Author(s)
      Hiroyuki Osada
    • Journal Title

      Biotechnology journal 5

      Pages: 724-727

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Phoslactomycn targets cysteine-269 of protein phosphatase 2A catalytic subunit2005

    • Author(s)
      Takayuki TERUYA
    • Journal Title

      FEBS letters 579

      Pages: 2463-2468

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Detection method for bimolecular interaction

    • Author(s)
      Naoki Kanoh
    • Journal Title

      International Patent PCT/JP2005/18841 (filed 10/13/2005)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] ナノバイオ計測の実際(第6章 小分子チップ)2007

    • Author(s)
      叶 直樹
    • Publisher
      講談社サイエンティフィク(印刷中)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 分子間相互作用解析ハンドブック(光親和型低分子マイクロアレイを用いた低分子-蛋白質相互作用の検出)2007

    • Author(s)
      齊藤安貴子
    • Publisher
      (株)羊土社(印刷中)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 相互作用観察法2005

    • Inventor(s)
      叶 直樹
    • Industrial Property Rights Holder
      理化学研究所
    • Filing Date
      2005-10-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 相互作用観察法2005

    • Inventor(s)
      叶 直樹
    • Industrial Property Rights Holder
      理化学研究所
    • Filing Date
      2005-10-17
    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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