期刊
PROTEIN AND PEPTIDE LETTERS
卷 19, 期 9, 页码 969-974出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/092986612802084465
关键词
Endostatin; lymphangiogenesis; peptide fragment; surface plasmon resonance; VEGF; VEGFR
资金
- NIH [EY021886, EY10101, EY01792]
- Midwest Eye Bank Research grant (Ann Arbor, Michigan)
- Research to Prevent Blindness (New York, NY)
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 x 10(7) M-1 s(-1), Kd of 0.6718 s(-1), and a K-D of 4.78 x 10(-8) M. 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.
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