title: Identification of VEGFR2-binding peptides using high throughput bacterial display methods and functional assessment.
abstract: The signal transduction pathway initiated by vascular endothelial growth factor-vascular endothelial growth factor receptor 2 (VEGF-VEGFR2) plays an important role in the angiogenesis of tumors. The effective antagonists of VEGFR2 would behave as potent drugs for the treatment of malignant cancers. In our study, specific binding peptides with high affinity to VEGFR2 were obtained through bacterial display technology. Conserved motif (FF/YEXWGVK) among those peptide sequences was discovered. One of the selected peptides, VRBP1 (YDGNSFYEMWGVKPASES) was identified by screening the biased bacterial peptide library and its physiochemical feature was further characterized. The results of surface plasmon resonance (SPR) assay indicated that the dissociation constant (KD) value of VRBP1 was 228.3 nM and this peptide competed with VEGF binding to VEGFR2. Particles conjugated with VRBP1 could recognize the human umbilical vein endothelial cells (HUVEC) which express VEGFR2 on the surface. Further therapeutic effect of VRBP1 was examined by in vivo experiments. VRBP1 could result in a significant decrease in tumor size of H460 xenografts. The results from the immunohistochemical assay showed that CD31 positive signals in VRBP1-treated group were fewer than those in the control ones. These data highlighted the potential of VEGFR2-binding peptides as effective molecules for cancer diagnosis and therapy.
authors: Kefeng
authors: K
authors: Pu
authors: Lihua
authors: L
authors: Yuan
authors: Lisha
authors: L
authors: Chen
authors: Anxin
authors: A
authors: Wang
authors: Xuan
authors: X
authors: Zhou
authors: Hailu
authors: H
authors: Zhang
authors: 398 Ruoshui Road, Suzhou Industrial Park, Suzhou 215123, China. ymzhu2008@sinano.ac.cn.
authors: Yimin
authors: Y
authors: Zhu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D057166:High-Throughput Screening Assays / Q000379:methods*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism; D019151:Peptide Library; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D010446:Peptide Fragments; D019151:Peptide Library; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2