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Targeting ALK1 using macrocyclic peptides: A novel approach for the regulation of angiogenesis in cancer

Research Project

Project/Area Number 17K15017
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor therapeutics
Research InstitutionUniversity of Tsukuba

Principal Investigator

Hipolito Chris  筑波大学, 医学医療系, 助教 (20759914)

Research Collaborator ten Dijke Peter  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsMacrocyclic peptides / In vitro selection / RaPID system / angiogenesis / macrocyclic peptide / ALK1 / BMP signaling / in vitro selection / macrocyclic peptides / ALK1 receptor / tumor angiogenesis / cancer signaling
Outline of Final Research Achievements

We performed the RaPID selection against the BMP receptor ALK1 and isolated the macrocyclic peptide ALK1-3R6-5. We characterized ALK1-R6-5 using biolayer interferometry, in vitro inhibition assays, and pull-down assays. Our conclusion is that ALK1-3R6-5 is too small for our experiments. I have produced a monobody library to address this problem. This library is based on the scaffold of fibronectin, which has a larger and better-defined structure. We have validated production of the library and are currently in the process of performing selection for ALK1-binding monobodies.

Academic Significance and Societal Importance of the Research Achievements

The significance of our findings brings us closer to inhibiting tumor growth in cancer. We learned that regulation of the ALK1 receptor and subsequent inhibition of angiogenesis requires a ligand larger than a macrocyclic peptide and we are now developing monobodies against ALK1.

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (4 results)

All 2018 2017 Other

All Int'l Joint Research (1 results) Presentation (2 results) Book (1 results)

  • [Int'l Joint Research] Leiden University Medical Center(オランダ)

    • Related Report
      2018 Annual Research Report
  • [Presentation] Identification of macrocyclic peptides which bind to CD442018

    • Author(s)
      Nohara Goto, Yizhen Yin, Christopher John Hipolito, Hiroyuki Suzuki, Hiroaki Suga, Mitsuyasu Kato, Paraskevi Heldin, Constantinos Kolliopoulos, Theodoros Karalis
    • Organizer
      10th International Peptide Symposium
    • Related Report
      2018 Annual Research Report
  • [Presentation] In vitro selection for macrocyclic peptide that regulate tumor angiogenesis and other ailments2017

    • Author(s)
      Christopher John Hipolito, Mitsuyasu Kato, Peter ten Dijke
    • Organizer
      TGFbeta Meeting
    • Related Report
      2017 Research-status Report
  • [Book] Methods in Molecular Biology2018

    • Author(s)
      Kusakizako T, Tanaka Y, Hipolito CJ, Suga H, Nureki O.
    • Total Pages
      21
    • Publisher
      Humana Press, New York, NY
    • ISBN
      9781493974528
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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