The expression of Vascular endothelial growth factors (VEGFs) is induced by hypoxia-inducible factors activated by the hypoxia. VEGF interacts with vascular endothelial growth factor receptor 2 (VEGFR-2) and mediates angiogenesis. Thus, inhibition of VEGFR-2 activity could be useful target for the treatment of abnormal angiogenesis, and antibody drugs against VEGFR-2 have been developed. However, antibody drugs are expensive because they are produced by mammalian cells. Therefore, it is important to develop VEGFR-2 binding agents such as peptides that can be chemically synthesized at low cost for angiogenesis-dependent diseases.
　Here, we report the PURE (protein synthesis using recombinant elements) system-based mRNA display evolution of unnatural cyclic peptides binding to the VEGFR-2 via genetic code expansion.