info:eu-repo/semantics/article
Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors
Fecha
2019-03Registro en:
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
2296-2646
CONICET Digital
CONICET
Autor
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
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.