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

Establishment of an all-complete chemical synthesis process producing 10 trillion peptide oligomers in one container.

Research Project

Project/Area Number 19K22272
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 38:Agricultural chemistry and related fields
Research InstitutionTokyo University of Agriculture and Technology

Principal Investigator

Chiba Kazuhiro  東京農工大学, (連合)農学研究科(研究院), 学長 (20227325)

Project Period (FY) 2019-06-28 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords核酸医薬 / 電解合成 / 化学合成 / 中分子 / ペプチド / 液相合成 / 電解反応 / 有機合成 / 生物活性 / コンビナトリアルケミストリー
Outline of Research at the Start

分子量が400~4,000程度の多様な中分子をいかにして確実に得るかということが,新たな有用物質ライブラリーとしての位置づけを確固たるものとするうえで極めて重要になっている.本研究は,逆ミセル反応法を飛躍的に発展させることによって,従前技術ではほぼ不可能であった10兆種類のペプチド等モル混合物を迅速かつ効率的に得るための新しい化学プロセスを確立することを目的とする.すなわち、申請者が独自に開発した逆ミセルを形成する可溶性タグに対しアミノ酸をランダムに10回反応させることにより,1容器内に10merのペプチド全理論数である10兆種類を定量的に得ることを目指す.

Outline of Final Research Achievements

The first amino acid is bound to a bead-shaped resin, and then amino acids are successively bound to the beads in sequence order (solid-phase synthesis). This method is widely used to synthesise specific target peptides as designed. In this study, we aim to establish a new liquid-phase synthesis method that utilises the advantages of the solid-phase synthesis method as an innovative chemical process that can accurately obtain all theoretical species as an equivalent mixture. To achieve this, a number of new challenges need to be overcome, and overcoming these challenges is a highly innovative research task that surpasses conventional technology.

Academic Significance and Societal Importance of the Research Achievements

.本研究は,これまでの方法の課題点を克服し,ほぼ無限に存在するペプチド分子について,体系的,網羅的,かつ定量的に完全化学合成を達成する革新的な提案である.本法を応用することにより、今後新たに発生する感染症対策や,新種の疾病,新規農薬用途などに対応した活性物質を探索するために極めて重要な役割をになう革新技術となるものである.

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (34 results)

All 2024 2022 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (15 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 15 results,  Open Access: 1 results) Presentation (17 results) (of which Int'l Joint Research: 8 results,  Invited: 2 results) Funded Workshop (1 results)

  • [Int'l Joint Research] The University of Tulsa/Department of Chemistry and Biochemistry(米国)

    • Related Report
      2022 Research-status Report
  • [Journal Article] Synthetic electrochemistry for peptides2024

    • Author(s)
      Okada Yohei、Chiba Kazuhiro
    • Journal Title

      Current Opinion in Electrochemistry

      Volume: 45 Pages: 101469-101469

    • DOI

      10.1016/j.coelec.2024.101469

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design, synthesis and biological evaluation of simplified analogues of MraY inhibitory natural product with rigid scaffold2022

    • Author(s)
      Kazuhiro, Okamoto; Aoi, Ishikawa; Ryotaro, Okawa; Kazuki, Yamamoto; Toyotaka, Sato; Shinichi, Yokota; Kazuhiro, Chiba; Satoshi, Ichikawa
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 55 Pages: 116556-116556

    • DOI

      10.1016/j.bmc.2021.116556

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Direct Anodic <i>N</i> ‐α Hydroxylation: Accessing Versatile Intermediates for Azanucleoside Derivatives2022

    • Author(s)
      Kurose Yuma、Okamoto Kazuhiro、Okada Yohei、Kitano Yoshikazu、Chiba Kazuhiro
    • Journal Title

      Asian Journal of Organic Chemistry

      Volume: accepted Issue: 4

    • DOI

      10.1002/ajoc.202100756

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oxidation Potential Gap (ΔEox): The Hidden Parameter in Redox Chemistry2022

    • Author(s)
      Okamoto, K.; Shida, N.; Morizumi, H.; Kitano, Y.; Chiba, K.
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 61 Issue: 30

    • DOI

      10.1002/anie.202206064

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Probing Electron Transfer Events in Radical Cation Cycloadditions: Intramolecular vs. Intermolecular Single Electron Transfer2022

    • Author(s)
      Tanami Shuhei、Hussaini Syed R.、Kitano Yoshikazu、Chiba Kazuhiro、Okada Yohei
    • Journal Title

      European Journal of Organic Chemistry

      Volume: 2022 Issue: 40

    • DOI

      10.1002/ejoc.202201023

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Stereoselective Production of Imino-D-ribitol and C-Azanucleosides via Electrochemical C-H Functionalization2022

    • Author(s)
      Morizumi, H.; Okamoto, K.; Akahane, S.; Takemae, H.; Oba, M.; Okada , Y.; Kitano, Y.; Mizutani, T.; Chiba, K.
    • Journal Title

      Eur. J. Org. Chem.

      Volume: 26 Issue: 1

    • DOI

      10.1002/ejoc.202201046

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Peptide Head‐to‐Tail Cyclization: A “Molecular Claw” Approach2021

    • Author(s)
      Yamagami, S.; Okada, Y.; Kitano, Y.; Chiba, K.
    • Journal Title

      Eur. J. Org. Chem.

      Volume: 22 Issue: 22 Pages: 3133-3138

    • DOI

      10.1002/ejoc.202100185

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Electrochemical Synthesis of Imino‐C‐Nucleosides by “Reactivity Switching” Methodology for in situ Generated Glycoside Donors2021

    • Author(s)
      Okamoto Kazuhiro, Tsutsui Mizuki, Morizumi Haruka, Kitano Yoshikazu, Chiba Kazuhiro
    • Journal Title

      European Journal of Organic Chemistry

      Volume: 印刷中 Issue: 17 Pages: 2479-2484

    • DOI

      10.1002/ejoc.202100106

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hydrosilane-Mediated Electrochemical Reduction of Amides2021

    • Author(s)
      Okamoto, K.; Nagahara, S.; Imada, Y.; Narita, R.; Kitano, Y.; Chiba, K.
    • Journal Title

      J. Org. Chem.

      Volume: 86 Issue: 22 Pages: 15992-16000

    • DOI

      10.1021/acs.joc.1c00931

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biphasic Electrochemical Peptide Synthesis2021

    • Author(s)
      Nagahara, S.; Okada, Y.; Kitano, Y.; Chiba, K.
    • Journal Title

      Chem. Sci.

      Volume: 12 Issue: 39 Pages: 12911-12917

    • DOI

      10.1039/d1sc03023j

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Electrochemical Amide Bond Formation from Benzaldehydes and Amines: Oxidation by Cathodic‐Generated Hydrogen Peroxide2020

    • Author(s)
      Kurose, Y.; Imada, Y.; Okada, Y.; Chiba, K.
    • Journal Title

      Eur. J. Org. Chem.

      Volume: 25 Issue: 25 Pages: 3844-3846

    • DOI

      10.1002/ejoc.202000479

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mechanistic Insights on Concentrated Lithium Salt/Nitroalkane Electrolyte Based on Analogy with Fluorinated Alcohols2020

    • Author(s)
      Naoki Shida, Yasushi Imada, Yohei Okada, Kazuhiro Chiba
    • Journal Title

      Eur. J. Org. Chem.

      Volume: 2020 Issue: 5 Pages: 570-574

    • DOI

      10.1002/ejoc.201901576

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Electrochemical Formation of Cinnamaldehyde by the Electrolyte System N,N ‐Diisopropylethylamine and 1,1,1,3,3,3‐Hexafluoropropan‐2‐ol2020

    • Author(s)
      Imada Yasushi、Okada Yohei、Chiba Kazuhiro
    • Journal Title

      ChemElectroChem

      Volume: 7 Issue: 7 Pages: 1619-1622

    • DOI

      10.1002/celc.202000275

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Electrochemical Total Synthesis of Pyrrolophenanthridone Alkaloids: Controlling for the Anodically Initiated Electron Transfer Process2020

    • Author(s)
      Kazuhiro Okamoto, Kazuhiro Chiba
    • Journal Title

      Org. Lett.

      Volume: 22 Issue: 9 Pages: 3613-3617

    • DOI

      10.1021/acs.orglett.0c01082

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Improved Tag-Assisted Liquid-Phase Peptide Synthesis: Application to the Synthesis of the Bradykinin Receptor Antagonist Icatibant Acetate2019

    • Author(s)
      Yohei Okada, Rico Takasawa, Daisuke Kubo, Natsumi Iwanaga, Shuji Fujita, Kosuke Suzuki, Hideaki Suzuki, Hidehiro Kamiya, Kazuhiro Chiba,
    • Journal Title

      Org. Process Res. Dev.

      Volume: 23 Issue: 11 Pages: 2576-2581

    • DOI

      10.1021/acs.oprd.9b00397

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 電解発生イミニウムカチオン種の構造解析および反応性制御に基づくイミノ糖C-グリコシド類の合成2021

    • Author(s)
      岡本一央,筒井瑞季,北野克和,千葉一裕
    • Organizer
      日本農薬学会第46 回大会
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] つくる責任つかう責任と有機合成反応2021

    • Author(s)
      千葉一裕
    • Organizer
      日本農薬学会第46 回大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Electrochemical Total Synthesis of Kalbretorine2020

    • Author(s)
      Kazuhiro Okamoto and Kazuhiro Chiba
    • Organizer
      14th International Symposium on Organic Reactions
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Electrochemical Peptide Synthesis Utilizing Soluble-Tag Method2020

    • Author(s)
      Shingo Nagahara1, Yohei Okada2 and Kazuhiro Chiba
    • Organizer
      14th International Symposium on Organic Reactions
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of Intramolecular Peptide Cyclization Method without Intermolecular cyclization reactions2020

    • Author(s)
      Sayuri Yamagami,1 Yohei Okada,2 Yoshikazu Kitano,1 and Kazuhiro Chiba
    • Organizer
      14th International Symposium on Organic Reactions
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Regioselective Deacetylation of Tetra-O-Acetyl-D-Mannose by Broensted Acid-Mediated Intramolecular Rearrangement2020

    • Author(s)
      Ryota Kai, Kazuhiro Okamoto and Kazuhiro Chiba
    • Organizer
      14th International Symposium on Organic Reactions
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Electrochemical Amide Bond Formation from Benzaldehydes and Amines:Oxidation by Cathodic-Generated Hydrogen Peroxide2020

    • Author(s)
      Yuma Kurose, Yasushi Imada, Yohei Okada, and Kazuhiro Chiba
    • Organizer
      14th International Symposium on Organic Reactions
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Nitromethylation of Amino Acids by Paired Electrolysis in MeNO2-LiClO42020

    • Author(s)
      Masato Kashiwazaki, Atsuro Ito, Kazuhiro Okamoto and Kazuhiro Chiba
    • Organizer
      14th International Symposium on Organic Reactions
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] A New Method for the Preparation of Bis(alkylamino)maleonitriles from Aliphatic Isocyanides2020

    • Author(s)
      Takaya Fujihara, Sayaka Tafuku, Takuya Fukuda, Kazuhiro Chiba and Yoshikazu Kitano
    • Organizer
      14th International Symposium on Organic Reactions
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 電解C-グリコシド結合形成によるC-Azanucleosideの合成2020

    • Author(s)
      筒井瑞季、岡本一央、千葉一裕
    • Organizer
      日本化学会春季年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 可溶性タグを利用した電気化学的ペプチド合成法の開発2020

    • Author(s)
      永原紳吾、岡田洋平、千葉一裕
    • Organizer
      日本化学会春季年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 大量合成に適したペプチド液相合成法の開発2020

    • Author(s)
      高澤 理子、岡田 洋平、久保 大輔、岩永 なつみ、藤田 秀司、鈴木 康介、鈴木 秀明、神谷 秀博、千葉 一裕
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 分子内電子移動過程の制御による Pratosine の電解全合成2020

    • Author(s)
      岡本 一央、千葉 一裕
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ペプチドの分子内環化反応を促進する反応場の構築2020

    • Author(s)
      山上 紗弓理、岡田 洋平、北野 克和、千葉 一裕
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 農芸化学の世界から未来を拓くために2020

    • Author(s)
      千葉 一裕
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 過塩素酸リチウム-ニトロアルカン系における陽極酸化を鍵反応としたヌクレオシドアナログの合成研究2019

    • Author(s)
      岡本一央、信田尚毅、筒井瑞季、小路貴生、千葉一裕
    • Organizer
      第43回有機電子移動化学討論会
    • Related Report
      2019 Research-status Report
  • [Presentation] 可溶性タグを利用した電気化学的ペプチド合成法の開発2019

    • Author(s)
      永原紳吾、千葉一裕
    • Organizer
      第43回有機電子移動化学討論会
    • Related Report
      2019 Research-status Report
  • [Funded Workshop] The 14th International Symposium on Organic Reactions, the 44th Symposium on Organic Electron Transfer Chemistry (EOC), and the 8th German Japanese (Global Joint) Symposium on Electrosynthesis2020

    • Related Report
      2020 Research-status Report

URL: 

Published: 2019-07-04   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi