title: Miniaturizing VEGF: Peptides mimicking the discontinuous VEGF receptor-binding site modulate the angiogenic response.
abstract: The angiogenic properties of VEGF are mediated through the binding of VEGF to its receptor VEGFR2. The VEGF/VEGFR interface is constituted by a discontinuous binding region distributed on both VEGF monomers. We attempted to reproduce this discontinuous binding site by covalently linking into a single molecular entity two VEGF segments involved in receptor recognition. We designed and synthesized by chemical ligation a set of peptides differing in length and flexibility of the molecular linker joining the two VEGF segments. The biological activity of the peptides was characterized in vitro and in vivo showing a VEGF-like activity. The most biologically active mini-VEGF was further analyzed by NMR to determine the atomic details of its interaction with the receptor.
authors: Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134, Napoli, Italy.
authors: Lucia
authors: L
authors: De Rosa
authors: Dipartimento di Scienze della Vita, Università di Siena, Via A. Moro 2, 53100 Siena, Italy.
authors: Federica
authors: F
authors: Finetti
authors: Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134, Napoli, Italy.
authors: Donatella
authors: D
authors: Diana
authors: Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134, Napoli, Italy.
authors: Rossella
authors: R
authors: Di Stasi
authors: Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134, Napoli, Italy.
authors: Sara
authors: S
authors: Auriemma
authors: Dipartimento di Farmacia, Università di Napoli "Federico II", via Mezzocannone 16, 80134, Napoli, Italy.
authors: Alessandra
authors: A
authors: Romanelli
authors: Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, via A. Vivaldi 43, 81100, Caserta, Italy.
authors: Roberto
authors: R
authors: Fattorusso
authors: Dipartimento di Scienze della Vita, Università di Siena, Via A. Moro 2, 53100 Siena, Italy.
authors: Marina
authors: M
authors: Ziche
authors: Dipartimento di Scienze della Vita, Università di Siena, Via A. Moro 2, 53100 Siena, Italy.
authors: Lucia
authors: L
authors: Morbidelli
authors: Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134, Napoli, Italy.
authors: Luca Domenico
authors: LD
authors: D'Andrea
mesh_terms: D000818:Animals; D001665:Binding Sites; D002465:Cell Movement; D049109:Cell Proliferation; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; C000588866:KDR protein, human; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2