Molecular modelling, synthesis and biological evaluation of peptide inhibitors as anti-angiogenic agent targeting neuropilin-1 for anticancer application.
Fiche publication
Date publication
janvier 2017
Journal
Journal of biomolecular structure & dynamics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BARBERI-HEYOB Muriel, Dr FROCHOT Céline, Dr VANDERESSE Régis, Pr BOURA Cédric
Tous les auteurs :
Kamarulzaman EE, Vanderesse R, Gazzali AM, Barberi-Heyob M, Boura C, Frochot C, Shawkataly O, Aubry A, Wahab HA
Lien Pubmed
Résumé
Vascular endothelial growth factor (VEGF) and its co-receptor neuropilin-1 (NRP-1) are important targets of many pro-angiogenic factors. In this study, nine peptides were synthesized and evaluated for their molecular interaction with NRP-1 and compared to our previous peptide ATWLPPR. Docking study showed that the investigated peptides shared the same binding region as shown by tuftsin known to bind selectively to NRP-1. Four pentapeptides (DKPPR, DKPRR, TKPPR and TKPRR) and a hexapeptide CDKPRR demonstrated good inhibitory activity against NRP-1. In contrast, peptides having arginine residue at sites other than the C-terminus exhibited low activity towards NRP-1 and this is confirmed by their inability to displace the VEGF165 binding to NRP-1. Docking study also revealed that replacement of carboxyl to amide group at the C-terminal arginine of the peptide did not affect significantly the binding interaction to NRP-1. However, the molecular affinity study showed that these peptides have marked reduction in the activity against NRP-1. Pentapeptides having C-terminal arginine showed strong interaction and good inhibitory activity with NRP thus may be a good template for anti-angiogenic targeting agent.
Mots clés
Amino Acid Sequence, Angiogenesis Inhibitors, chemistry, Antineoplastic Agents, chemistry, Binding Sites, Drug Design, Humans, Ligands, Models, Molecular, Molecular Conformation, Molecular Docking Simulation, Molecular Dynamics Simulation, Neuropilin-1, antagonists & inhibitors, Peptides, chemistry, Protein Binding, Vascular Endothelial Growth Factor A, antagonists & inhibitors
Référence
J. Biomol. Struct. Dyn.. 2017 Jan;35(1):26-45