Targeting VEGF receptors with non-neutralizing cyclopeptides for imaging applications.

Abstract

Pharmacological strategies aimed at preventing cancer growth are in most cases paralleled by diagnostic investigations for monitoring and prognosticating therapeutic efficacy. A relevant approach in cancer is the suppression of pathological angiogenesis, which is principally driven by vascular endothelial growth factor (VEGF) or closely related factors and by activation of specific receptors, prevailingly VEGFR1 and VEGFR2, set on the surface of endothelial cells. Monitoring the presence of these receptors in vivo is henceforth a way to predict therapy outcome. We have designed small peptides able to bind and possibly antagonize VEGF ligands by targeting VEGF receptors. Peptide systems have been designed to be small, cyclic and to host triplets of residues known to be essential for VEGF receptors recognition and we named them 'mini-factors'. They have been structurally characterized by CD, NMR and molecular dynamics (MD) simulations. Mini-factors do bind with different specificity and affinity VEGF receptors but none blocks receptor activity. Following derivatization with suitable tracers they have been employed as molecular probes for sensing receptors on cell surface without affecting their activity as is usually observed with other binders having neutralizing activity.

• Authors: Luisa Calvanese, Andrea Caporale, Giuseppina Focà, Emanuela Iaccarino, Annamaria Sandomenico, Nunzianna Doti, Ivana Apicella, Giuseppina Maria Incisivo, Sandro De Falco, Lucia Falcigno, Gabriella D'Auria, Menotti Ruvo
• Journal: Amino acids (Amino Acids) Vol. 50 Issue 2 Pg. 321-329 (02 2018) ISSN: 1438-2199 [Electronic] Austria
• PMID: 29198078 (Publication Type: Journal Article)

Chemical References

• Disulfides
• Oligopeptides
• Peptide Library
• Recombinant Proteins
• FLT1 protein, human
• KDR protein, human
• Receptors, Vascular Endothelial Growth Factor
• Vascular Endothelial Growth Factor Receptor-1
• Vascular Endothelial Growth Factor Receptor-2

Topics

• Biotinylation
• Disulfides (chemistry)
• Dose-Response Relationship, Drug
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• HEK293 Cells
• Humans
• Magnetic Resonance Imaging
• Models, Molecular
• Oligopeptides (chemistry, metabolism)
• Peptide Library
• Protein Binding
• Receptors, Vascular Endothelial Growth Factor (metabolism)
• Recombinant Proteins (metabolism)
• Surface Plasmon Resonance
• Vascular Endothelial Growth Factor Receptor-1 (metabolism)
• Vascular Endothelial Growth Factor Receptor-2 (metabolism)