Selective Binding of Endostatin Peptide 4 to Recombinant VEGF Receptor 3 In Vitro.
We previously reported that neostatin, a proteolytic fragment of collagen XVIII that includes endostatin, inhibits basic fibroblast growth factor-induced corneal angiogenesis and lymphangiogenesis. In experiments to determine which fragments in neostatin are responsible for binding to VEGF receptors (VEGFRs), we previously showed that a 28- mer sequence at the C-terminal of endostatin, known as endostatin peptide 9, preferentially binds VEGFR3-Fc over VEGFR1-Fc and VEGFR2-Fc. In the present study, we show that a different endostatin fragment, endostatin peptide 4 (26 mers long), also selectively binds VEGFR3-Fc and not VEGFR1-Fc or VEGFR2-Fc. From surface plasmon resonance data, the KD and Chi² (RU²) values for endostatin peptide 4 binding to VEGFR3-Fc are 5.72 × 10⁻⁸ M and 0.354, respectively. In conclusion, endostatin peptides 4 and 9 may be responsible for endostatin binding to VEGFR3-Fc, and this improved understanding of endostatin peptide binding to VEGFR3-Fc may support the development of therapeutics targeting lymphangiogenic processes.
Kyu-Yeon
KY
Han
Michael
M
Chang
Hong-Yu
HY
Ying
Hyun
H
Lee
Yu-Hui
YH
Huang
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 W. Taylor Street, Chicago, IL 60612, USA. changr@uic.edu.
Jin-Hong
JH
Chang
Dimitri T
DT
Azar
D000595:Amino Acid Sequence; D043170:Collagen Type XVIII; D043169:Endostatins / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000737:chemistry* / Q000378:metabolism*
D043170:Collagen Type XVIII; D043169:Endostatins; D011994:Recombinant Proteins; D040321:Vascular Endothelial Growth Factor Receptor-3