Affiliations 

  • 1 a School of Pharmaceutical Sciences , Universiti Sains Malaysia , 11800 Penang , Malaysia
  • 2 b LCPM, UMR-CNRS 7375, Université de Lorraine, ENSIC , 1 Rue Grandville, F-54000 Nancy , France
  • 3 c CRAN, UMR-CNRS 7039 , Campus Science, BP 70239, F-54506 Vandœuvre-lès-Nancy , France
  • 4 d LRGP , UMR-CNRS 7274, Université de Lorraine, ENSIC , 1 Rue Grandville, F-54000 Nancy , France
  • 5 e Chemical Sciences Programme , School of Distance Education, Universiti Sains Malaysia , 11800 Penang , Malaysia
J Biomol Struct Dyn, 2017 Jan;35(1):26-45.
PMID: 26766582 DOI: 10.1080/07391102.2015.1131196

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.