VEGF receptors have been the target of intense research aimed to develop molecules able to inhibit or stimulate angiogenesis. Based on the x-ray structure of the complex Placenta growth factor-VEGF Receptor 1D2, we designed a VEGF receptor binding peptide reproducing the PlGF β-hairpin region Gln87-Val100 which is involved in receptor recognition. A conformational analysis showed that the designed peptide adopts the expected fold in pure water. Moreover, a combination of NMR interaction analysis and cell binding studies were used to demonstrate that the peptide targets VEGF receptors. The VEGFR1D2 interacting residues were characterized at molecular level and they correspond to the residues recognizing the PlGF sequence Gln87-Val100. Finally, the peptide biological activity was characterized in vitro and in vivo showing a VEGF-like behavior. Indeed, the peptide activates VEGF-dependent intracellular pathways, induces endothelial cell proliferation, rescue from apoptosis and promotes angiogenesis in vivo. This compound is one of the few peptides known with proangiogenic activity which makes it a candidate for the development of novel peptide-based drug for medical applications in therapeutic angiogenesis.

{beta}-hairpin peptide targeting VEGF receptors: design, NMR characterization and biological activity.

BASILE, ANNA;TURCO, Maria Caterina;
2011-01-01

Abstract

VEGF receptors have been the target of intense research aimed to develop molecules able to inhibit or stimulate angiogenesis. Based on the x-ray structure of the complex Placenta growth factor-VEGF Receptor 1D2, we designed a VEGF receptor binding peptide reproducing the PlGF β-hairpin region Gln87-Val100 which is involved in receptor recognition. A conformational analysis showed that the designed peptide adopts the expected fold in pure water. Moreover, a combination of NMR interaction analysis and cell binding studies were used to demonstrate that the peptide targets VEGF receptors. The VEGFR1D2 interacting residues were characterized at molecular level and they correspond to the residues recognizing the PlGF sequence Gln87-Val100. Finally, the peptide biological activity was characterized in vitro and in vivo showing a VEGF-like behavior. Indeed, the peptide activates VEGF-dependent intracellular pathways, induces endothelial cell proliferation, rescue from apoptosis and promotes angiogenesis in vivo. This compound is one of the few peptides known with proangiogenic activity which makes it a candidate for the development of novel peptide-based drug for medical applications in therapeutic angiogenesis.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11386/3066327
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