Polypeptides targeting vascular endothelial growth factor receptor-2 and αvβ3 integrin

摘要

Polypeptides comprising variant vascular endothelial growth factor sequences are provided. The polypeptides are useful in cancer imaging, cancer diagnosis, monitoring and treatment as well as treatment of diseases characterized by excessive neovascularization.

主权项

1. A human vascular endothelial growth factor (VEGF) variant polypeptide, comprising:
a first human VEGF polypeptide comprising F17A and E64A substitutions, and linked through a polypeptide linker to a second human VEGF polypeptide comprising I46A mutation, wherein said second human VEGF polypeptide comprises an integrin-recognition RGD motif containing loop selected from the sequences set forth in any one of SEQ ID NO:29-SEQ ID NO:75 and replacing a loop 3 sequence of said VEGF polypeptide to provide a single-chain VEGF antagonist, whereby the VEGF variant exhibits a high affinity to VEGF receptor-2 (VEGFR2) and alpha v beta 3 integrin.