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

Journal of Biomolecular Structure & Dynamics
Ezatul Ezleen KamarulzamanHabibah A Wahab

Abstract

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.

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Citations

Jun 26, 2018·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·L LarueC Frochot
Dec 19, 2019·Journal of Clinical Medicine·Zahraa YoussefCéline Frochot
Nov 24, 2020·International Journal of Nanomedicine·Mickaël GriesMuriel Barberi-Heyob
Dec 31, 2020·International Journal of Molecular Sciences·Anna K PuszkoAleksandra Misicka

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Methods Mentioned

BETA
ELISA
NMR
Enzyme-linked

Software Mentioned

LigPlot
FlexPrepDock
CABS
HyperChem Pro
HyperChem
dock
AutoDock
AutoDockTools ( ADT
HADDOCK
Rosetta

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