Artículo
Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors
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
Fecha de publicación:
03/2019
Editorial:
Frontiers Media S.A.
Revista:
Frontiers in Chemistry
ISSN:
2296-2646
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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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Articulos(CCT - SANTA FE)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - SANTA FE
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - SANTA FE
Citación
Zanella, Simone; Bocchinfuso, Gianfranco; De Zotti, Marta; Arosio, Daniela; Marino, Franca; et al.; Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors; Frontiers Media S.A.; Frontiers in Chemistry; 7; 3-2019; 1-13
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