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

[ Vol. 19 , Issue. 9 ]

Author(s):

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

Abstract:


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.

Keywords:

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

Affiliation:

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



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