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Article Dans Une Revue Journal of Biomolecular Structure and Dynamics Année : 2017

Molecular modelling, synthesis and biological evaluation of peptide inhibitors as anti-angiogenic agent targeting Neuropilin-1 for anticancer application

Résumé

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 neuropilin-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.

Domaines

Cancer

Dates et versions

hal-01309306 , version 1 (29-04-2016)

Identifiants

Citer

Ezatul E. Kamarulzaman, Régis Vanderesse, Amirah M. Gazzali, Muriel Barberi-Heyob, Cédric Boura, et al.. Molecular modelling, synthesis and biological evaluation of peptide inhibitors as anti-angiogenic agent targeting Neuropilin-1 for anticancer application. Journal of Biomolecular Structure and Dynamics, 2017, 35 (1), pp.26-45. ⟨10.1080/07391102.2015.1131196⟩. ⟨hal-01309306⟩
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