[Development of toxin targeting to VEGF-KDR].

OBJECTIVE:To develop toxin targeting vascular endothelial growth factor receptor II (VEGF-II/KDR) fused with a KDR-binling peptide screened from peptide library. METHODS:By affinity to KDR molecular which expressed specifically by new born vascular endothelial cell, peptides to KDR were screened from C7 peptide library by phage display. Among them, a peptide binding to KDR with high affinity termed as P5 was selected and fused to the N-terminal of Shiga toxin subunit A (StxA). The protein (P5-StxA) was expressed in E. coli. RESULTS:ELISA and Western blot were applied to characterize the binding interaction between the fusion protein, P5-StxA and KDR. Cytotoxicity assay showed that P5-StxA maintained similar toxicity to cell as StxA. In the model of angiogenesis, P5-StxA inhibited selectively VEGF-induced growth of preexisting vessels of the chick chorioallantoic membrane. CONCLUSION:These studies demonstrate the small peptide, P5, maybe be used as carrier of toxin targeting to KDR.