2018 Fiscal Year Final Research Report
Targeting ALK1 using macrocyclic peptides: A novel approach for the regulation of angiogenesis in cancer
| Project/Area Number |
17K15017
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor therapeutics
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Research Collaborator |
ten Dijke Peter
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Keywords | Macrocyclic peptides / In vitro selection / RaPID system / angiogenesis |
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| 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.
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| Free Research Field |
Medicine
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| 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.
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