Rational Design of Antiangiogenic Helical Oligopeptides Targeting the Vascular Endothelial Growth Factor Receptors
Copyright policy )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 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 Cα,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.
- University of Milan Italy
- University of Milan Italy
- National Research Council Italy
- National Scientific and Technical Research Council Argentina
- National Academies of Sciences, Engineering, and Medicine United States
helical folded peptides, HELICAL FOLDED PEPTIDES, protein-protein interactions, VEGF-C, ANGIOGENESIS, PROTEIN-PROTEIN INTERACTIONS, angiogenesis, Protein-protein interaction, C, Angiogenesis; C α,α -disubstituted amino acids ; Helical folded peptides; Protein-protein interactions; VEGF-C; Chemistry (all), CAlpha, https://purl.org/becyt/ford/1.4, C-alpha,C-alpha-disubstituted amino acids, https://purl.org/becyt/ford/1, QD1-999, Settore CHIM/02 - CHIMICA FISICA, -disubstituted amino acids, General Chemistry, helical folded peptides; protein-protein interactions; Calpha,alpha-disubstituted amino acids; VEGF-C; angiogenesis, Helical folded peptide, Angiogenesi, Angiogenesis; C ; α,α; -disubstituted amino acids ; Helical folded peptides; Protein-protein interactions; VEGF-C, Chemistry, α,α, Cα,α-disubstituted amino acids
helical folded peptides, HELICAL FOLDED PEPTIDES, protein-protein interactions, VEGF-C, ANGIOGENESIS, PROTEIN-PROTEIN INTERACTIONS, angiogenesis, Protein-protein interaction, C, Angiogenesis; C α,α -disubstituted amino acids ; Helical folded peptides; Protein-protein interactions; VEGF-C; Chemistry (all), CAlpha, https://purl.org/becyt/ford/1.4, C-alpha,C-alpha-disubstituted amino acids, https://purl.org/becyt/ford/1, QD1-999, Settore CHIM/02 - CHIMICA FISICA, -disubstituted amino acids, General Chemistry, helical folded peptides; protein-protein interactions; Calpha,alpha-disubstituted amino acids; VEGF-C; angiogenesis, Helical folded peptide, Angiogenesi, Angiogenesis; C ; α,α; -disubstituted amino acids ; Helical folded peptides; Protein-protein interactions; VEGF-C, Chemistry, α,α, Cα,α-disubstituted amino acids
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