Characterization of the interaction between endostatin short peptide and VEGF receptor 3

Corneal angiogenesis and lymphangiogenesis are induced by vascular endothelial growth factors (vegfs) signaling through its receptors vegfr-1,-2,and-3. endostatin is a peptide antagonist of these receptors that causes inhibition of bfgf-induced corneal angiogenesis and lymphangiogenesis. here we show that binding of vegf-c and endostatin to recombinant vegfr-3 is competitive. alignments of the primary amino acid sequences of vegf-c and the c-terminal endostatin peptide (mep: leqkaaschnsyivlciensfmtsfsk) identified two conserved cysteine residues separated by seven amino acids. peptides of vegf-c and mep containing these conserved residues bound tovegfr-3. however,substitution of alanine for either of the cysteines in the mep peptide perturbed the secondary structure,and this mutated peptide was unable to bind to vegfr-3. analysis by surface plasmon resonance demonstrated that the binding of the mep peptide for recombinant vegfr-3 had a ka of 1.41×10 7m-1s-1,kd of 0.6718 s-1,and a kd of 4.78×10-8m. characterization of the mechanism of endostatin binding to vegfr-3 may lead to the development of novel therapies for lymphangiogenesis-related disorders,such as transplant rejection,lymphedema,and cancer metastasis. © 2012 bentham science publishers.