Submit Manuscript  

Article Details

Characterization of the Interaction Between Endostatin Short Peptide and VEGF Receptor 3

[ Vol. 19 , Issue. 9 ]


Kyu-Yeon Han, Dimitri T. Azar, Abdellah Sabri, Hyun Lee, Sandeep Jain, Bao-Shiang Lee and Jin-Hong Chang   Pages 969 - 974 ( 6 )


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 1.41x107M-1s-1, Kd of 0.6718 s-1, and a KD of 4.78x10-8M. 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.


Endostatin, lymphangiogenesis, peptide fragment, surface plasmon resonance, VEGF, VEGFR


Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 W. Taylor Street, Chicago, IL60612.

Read Full-Text article