Controlling ligand surface density on streptavidin-magnetic particles by a simple, rapid, and reliable chemiluminescent test

International audienc

Helical peptides from VEGF and Vammin hotspots for modulating the VEGF-VEGFR interaction

The design, synthesis, conformational studies and binding affinity for VEGF receptors of a collection of linear and cyclic peptide analogues of the N-terminal α-helix fragments 13-25 of VEGF and 1-13 of Vammin are described. Linear 13(14)-mer peptides were designed with the help of an AGADIR algorithm and prepared following peptide solid-phase synthetic protocols. Cyclic peptide derivatives were prepared on-resin from linear precursors with conveniently located Glu and Lys residues, by the formation of amide linkages. Conformational analysis, CD and NMR, showed that most synthesized peptides have a clear tendency to be structured as α-helices in solution. Some of the peptides were able to bind a VEGFR-1 receptor with moderate affinity. In addition to the described key residues (Phe17, Tyr21 and Tyr25), Val14 and Val20 seem to be relevant for affinity.Peer Reviewe

Inhibition of VEGF/VEGFR1 interaction by a series of C-terminal modified cyclic peptides

Inhibition of the interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) is a validated therapeutic strategy of anti-cancer treatment. This approach consists in indirect blockage of the kinase activity on VEGFR with inhibitors of protein-protein interactions, which showed great interests in oncology. The FDA approved anti-cancer agents bevacizumab (Avastin®) and ziv-aflibercept (Zaltrap®) bind specifically to VEGF are from anti-VEGF strategy. The very recently approved agent ramucirumab (Cyramza®), a recombinant humanized monoclonal antibody that specifically binds to VEGFR2 is from anti-VEGFR strategy. Based on a cyclic peptide antagonist of VEGFR1 designed from VEGF fragments, we developed, by a new synthesis process, a series of C-terminal modified cyclic peptides to improve their receptor binding ability. Three of such peptides with aromatic groups showed greatly increased VEGFR1 binding affinity in a competition ELISA-based test. This research highlight discusses the processing and findings of the recent study

Design and Synthesis of C-Terminal Modified Cyclic Peptides as VEGFR1 Antagonists

Previously designed cyclic peptide antagonist c[YYDEGLEE]-NH2 disrupts the interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFRs). It represents a promising tool in the fight against cancer and age-related macular degeneration. We described in this paper the optimization of the lead peptide by C-terminal modification. A new strategy for the synthesis of cyclic peptides is developed, improving the cyclisation efficiency. At 100 µM, several new peptides with an aromatic group flexibly linked at C-terminal end showed significantly increased receptor binding affinities in competition ELISA test. The most active peptide carrying a coumarin group may be a useful tool in anti-angiogenic biological studies

Colorimetric immunoassays for the screening and specificity evaluation of molecules disturbing VEGFs/VEGFRs interactions

International audienc

Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF13-25 Fragment

The interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFR) has important implications in angiogenesis and cancer, which moved us to search for peptide derivatives able to block this protein–protein interaction. In a previous work we had described a collection of linear 13-mer peptides specially designed to adopt helical conformations (Ac-SSEEX5ARNX9AAX12N-NH2), as well as the evaluation of seven library components for the inhibition of the interaction of VEGF with its Receptor 1 (VEGFR1). This study led to the discovery of some new, quite potent inhibitors of this protein–protein system. The results we found prompted us to extend the study to other peptides of the library. We describe here the evaluation of a new selection of peptides from the initial library that allow us to identify new VEGF-VEGFR1 inhibitors. Among them, the peptide sequence containing F, W, and I residues at the 5, 9, and 12 positions, show a very significant nanomolar IC50 value, competing with VEGF for its receptor 1, VEGFR1 (Flt-1), which could represent a new tool within the therapeutic arsenal for cancer detection and therapy

Disrupting vegf-vegfr1 interaction: De novo designed linear helical peptides to mimic the VEGF13-25 Fragment

The interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFR) has important implications in angiogenesis and cancer, which moved us to search for peptide derivatives able to block this protein-protein interaction. In a previous work we had described a collection of linear 13-mer peptides specially designed to adopt helical conformations (Ac-SSEEXARNXAAXN-NH), as well as the evaluation of seven library components for the inhibition of the interaction of VEGF with its Receptor 1 (VEGFR1). This study led to the discovery of some new, quite potent inhibitors of this protein-protein system. The results we found prompted us to extend the study to other peptides of the library. We describe here the evaluation of a new selection of peptides from the initial library that allow us to identify new VEGF-VEGFR1 inhibitors. Among them, the peptide sequence containing F,W, and I residues at the 5, 9, and 12 positions, show a very significant nanomolar IC50 value, competing with VEGF for its receptor 1, VEGFR1 (Flt-1), which could represent a new tool within the therapeutic arsenal for cancer detection and therapy.This work was supported by the Spanish Ministerio de Economía y Competitividad (MINECO) SAF2015-66275-C2-R, subprograma NEF and by the University Paris Descartes and the ANR (Grants ANR-2010-BLANC-1533-03). BBP thanks the CSIC for a predoctoral fellowship (JAE-Predoc from Junta para la Ampliación de Estudios, co-financed by FSE).Peer Reviewe