[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.


CONCLUSIONS
These studies demonstrate the small peptide, P5, maybe be used as carrier of toxin targeting to KDR.
Wu
Jie
J
Medical Research Department, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
Chen
Hui-peng
HP
Zhang
Hong-bin
HB
Wang
Jie
J
Yang
Tai-cheng
TC
Xian
Jiang
J
Yang
Chuan-hong
CH
Lai
Huang-wen
HW
Wang
Qing-ming
QM
Zheng
Wen-ling
WL
D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D019151:Peptide Library; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D022621:Shiga Toxin / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D019151:Peptide Library; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D022621:Shiga Toxin; D040301:Vascular Endothelial Growth Factor Receptor-2