Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors

Tumor angiogenesis, essential for cancer development, is regulated mainly by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs), which are overexpressed in cancer cells. Therefore, the VEGF/VEGFR interaction represents a promising pharmaceutical target to fight cancer progressi...

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Detalles Bibliográficos
Autores: Zanella, Simone, Bocchinfuso, Gianfranco, De Zotti, Marta, Arosio, Daniela, Marino, Franca, Raniolo, Stefano, Pignataro, Luca, Sacco, Giovanni, Palleschi, Antonio, Siano, Alvaro Sebastían, Piarulli, Umberto, Belvisi, Laura, Formaggio, Fernando, Gennari, Cesare, Stella, Lorenzo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/104696
Acceso en línea:http://hdl.handle.net/11336/104696
Access Level:acceso abierto
Palabra clave:ANGIOGENESIS
CAlpha
HELICAL FOLDED PEPTIDES
PROTEIN-PROTEIN INTERACTIONS
VEGF-C
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
Descripción
Sumario:Tumor angiogenesis, essential for cancer development, is regulated mainly by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs), which are overexpressed in cancer cells. Therefore, the VEGF/VEGFR interaction represents a promising pharmaceutical target to fight cancer progression. The VEGF surface interacting with VEGFRs comprises a short α-helix. In this work, helical oligopeptides mimicking the VEGF-C helix were rationally designed based on structural analyses and computational studies. The helical conformation was stabilized by optimizing intramolecular interactions and by introducing helix-inducing C α,α -disubstituted amino acids. The conformational features of the synthetic peptides were characterized by circular dichroism and nuclear magnetic resonance, and their receptor binding properties and antiangiogenic activity were determined. The best hits exhibited antiangiogenic activity in vitro at nanomolar concentrations and were resistant to proteolytic degradation.

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