2018 Fiscal Year Annual Research Report
Targeting ALK1 using macrocyclic peptides: A novel approach for the regulation of angiogenesis in cancer
| Project/Area Number |
17K15017
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2017-04-01 – 2019-03-31
|
| Keywords | macrocyclic peptide / ALK1 / BMP signaling / angiogenesis |
|---|
| Outline of Annual Research Achievements |
We performed the RaPID selection against the BMP receptor ALK1 and isolated the macrocyclic peptide ALK1-3R6-5. Using biolayer interferography and confirmed that this peptide was not capable to bind strongly to ALK1. We continued to perform additional in vitro inhibition assays and although initial results showed some promise, ultimately the macrocyclic peptide was deemed inferior to nanobodies. I observed a trend where the the success of an in vitro selection appears to be related to the size of the target protein. In brief, ALK1 is too small to use in an in vitro selection for a high affinity macrocyclic peptide ligand. In light of this revelation, we developed libraries of peptides that are larger and have defined scaffolds.
|
