Abstract
Cancer angiogenesis is mainly initiated by vascular endothelial growth factors (VEGFs). On the basis of the reported crystal structures of three natural ligands (VEGF-A, -B, and PlGF) with the major receptors VEGFR-1 and VEGFR-2, we scanned receptor-binding epitopes of these ligands by designing linear and cyclic peptides with the aim to disrupt the VEGF-A/VEGFR-1 interaction, which is implicated in cancer development. The ability of peptides to inhibit this interaction was evaluated by an ELISA-based assay. Several peptides, especially those mimicking loop 1 (L1) of these ligands that binds primarily to domain D3 of VEGFRs, have demonstrated higher inhibition for VEGF-A/VEGFR-1 binding. They have also shown inhibitory effects on VEGF-induced tube formation in HUVECs (human umbilical vein endothelial cells). These results validate the domain D3 of VEGFRs as an efficient target for the design of VEGFR antagonists.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / chemistry
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Angiogenesis Inhibitors / pharmacology*
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Drug Design
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Epitopes / chemistry
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Human Umbilical Vein Endothelial Cells
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Humans
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Ligands
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Membrane Proteins / chemistry
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Peptide Fragments / chemistry
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Peptide Fragments / pharmacology*
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Peptides / chemistry
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Peptides / pharmacology*
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Peptides, Cyclic / chemistry
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Peptides, Cyclic / pharmacology
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Protein Domains
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Vascular Endothelial Growth Factor A / chemistry
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Vascular Endothelial Growth Factor B / chemistry
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Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors*
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Vascular Endothelial Growth Factor Receptor-1 / chemistry
Substances
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Angiogenesis Inhibitors
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Epitopes
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Ligands
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Membrane Proteins
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PIGF protein, human
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Peptide Fragments
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Peptides
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Peptides, Cyclic
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VEGFA protein, human
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VEGFB protein, human
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factor B
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Vascular Endothelial Growth Factor Receptor-1