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ペプチドセレクションによる酵素ミミック創薬のための戦略

Research Project

Project/Area Number 18F18727
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section外国
Research Field Bio-related chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

菅 裕明  東京大学, 大学院理学系研究科(理学部), 教授 (00361668)

Co-Investigator(Kenkyū-buntansha) TSIAMANTAS CHRISTOS  東京大学, 大学院理学系研究科, 外国人特別研究員
Project Period (FY) 2018-07-25 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2018: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsFIT system / Foldamers / Macrocyclic peptides
Outline of Annual Research Achievements

This work has harvested the potential of flexizymes (artificial aminoacylation ribozymes) coupled to an in vitro translation system (the “flexible” in vitro translation system, FIT), led to the ribosomal incorporation of the largest and bulkiest residues to date. Briefly, foldamers -molecules with a strong tendency to adopt a folded conformation- composed of aromatic oligoamides have been recently proven capable of initiating translation, yielding the first-of-their-kind foldamer-peptide-hybrids. In our current work, we expanded the repertoire of foldamer functionalities and have demonstrated that side-chain modification of the helical structures grants access to previously inaccessible chemical and structural space. The incorporation of both the bulkiest and largest single residues that have been introduced by the ribosome has been demonstrated. Additionally, intrigued by the ribosomal tolerance towards aromatic oligoamides during translation initiation, we advanced our investigations and explored the possibility of incorporating these abiotic molecules as appendages during translation elongation. Our results indicated that the incorporation of an amino acid residue with a foldamer on the side-chain, as long as a heptapeptide, is feasible. It demonstrates for the first time the tolerance of the ribosome towards residues of that size and expands the current understanding on the limitations of the translational machinery. The above studies have paved the way towards the introduction of foldamers into mRNA display for the discovery of functional foldamer-peptide hybrids.

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

Report

(1 results)
  • 2018 Annual Research Report
  • Research Products

    (6 results)

All 2018 Other

All Int'l Joint Research (1 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 3 results) Remarks (1 results)

  • [Int'l Joint Research] Ludwig Maximilian University of Munich(ドイツ)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] In vitro expression of genetically encoded non-standard peptides consisting of exotic amino acid building blocks.2018

    • Author(s)
      Hirose H, Tsiamantas C, Katoh T, Suga H.
    • Journal Title

      Curr Opin Biotechnol. 2018 Nov 16;58:

      Volume: 58 Pages: 28-36

    • DOI

      10.1016/j.copbio.2018.10.012

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] In Vitro Selection of aromatic oligoamide foldamers2018

    • Author(s)
      Tsiamantas Christos
    • Organizer
      Bordeaux Symposium on Foldamers
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ribosomally synthesized foldamer-containing peptides2018

    • Author(s)
      Tsiamantas Christos
    • Organizer
      4th International Conference on Circular Proteins and Peptides
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In Vitro Translated Peptide-Foldamer Hybrid Macrocycles2018

    • Author(s)
      Tsiamantas Christos
    • Organizer
      10th International Peptide Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 東京大学大学院理学系研究科化学専攻菅研究室ホームページ

    • URL

      https://www.chem.s.u-tokyo.ac.jp/users/bioorg/index.html

    • Related Report
      2018 Annual Research Report

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Published: 2018-07-26   Modified: 2024-03-26  

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