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.

Zanella, S., Bocchinfuso, G., De Zotti, M., Arosio, D., Marino, F., Raniolo, S., et al. (2019). Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors. FRONTIERS IN CHEMISTRY, 7, 170 [10.3389/fchem.2019.00170].

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

Bocchinfuso G.;Palleschi A.;Stella L.
2019-01-01

Abstract

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.
2019
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore CHIM/02 - CHIMICA FISICA
English
Angiogenesis; C ; α,α; -disubstituted amino acids ; Helical folded peptides; Protein-protein interactions; VEGF-C
https://www.frontiersin.org/articles/10.3389/fchem.2019.00170/full
Zanella, S., Bocchinfuso, G., De Zotti, M., Arosio, D., Marino, F., Raniolo, S., et al. (2019). Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors. FRONTIERS IN CHEMISTRY, 7, 170 [10.3389/fchem.2019.00170].
Zanella, S; Bocchinfuso, G; De Zotti, M; Arosio, D; Marino, F; Raniolo, S; Pignataro, L; Sacco, G; Palleschi, A; Siano, As; Piarulli, U; Belvisi, L; Formaggio, F; Gennari, C; Stella, L
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/218482
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