A small peptide derived from Flt-1 (VEGFR-1) functions as an angiogenic inhibitor.
Vascular endothelial growth factor (VEGF) is an angiogenic stimulator which functions through two endothelial specific tyrosine kinase receptors, Flt-1 and Flk-1. In this work, we show that an 11-amino acid peptide derived from the second immunoglobulin-like domain of Flt-1 functions as an angiogenic inhibitor in chick chorioallantoic membrane and inhibited VEGF-induced vascular permeability in Miles' assay without binding to VEGF directly. Circular dichroism and nuclear magnetic resonance analyses indicate that this peptide forms a stable extended structure in solution, presumably beta-sheet structure and is most likely existing as a dimer. Our results suggest that this small peptide functions as an angiogenic inhibitor by inhibiting VEGF function through a non-VEGF binding mechanism.
Tan
D C
DC
Department of Biological Sciences, National University of Singapore, Singapore 119260.
Kini
R M
RM
Jois
S D
SD
Lim
D K
DK
Xin
L
L
Ge
R
R
D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply / Q000187:drug effects; D002942:Circular Dichroism; D006224:Cricetinae; D019281:Dimerization; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D016326:Extracellular Matrix Proteins; D008222:Lymphokines; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1