Title:Characterization of the Interaction Between Endostatin Short Peptide and VEGF Receptor 3
Volume: 19
Issue: 9
Author(s): Kyu-Yeon Han, Dimitri T. Azar, Abdellah Sabri, Hyun Lee, Sandeep Jain, Bao-Shiang Lee and Jin-Hong Chang
Affiliation:
Keywords:
Endostatin, lymphangiogenesis, peptide fragment, surface plasmon resonance, VEGF, VEGFR
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.
