Design, synthesis and in vitro biological evaluation of a small cyclic peptide as inhibitor of vascular endothelial growth factor binding to neuropilin-1

Bioorg Med Chem Lett. 2016 Jun 15;26(12):2843-2846. doi: 10.1016/j.bmcl.2016.04.059. Epub 2016 Apr 21.

Abstract

Neuropilin-1 (NRP-1) is a co-receptor of VEGFR (vascular endothelial growth factor receptor), but it is also suggested that NRP-1 in tumour cells may serve as a separate receptor for VEGF165. Therefore molecules interfering with VEGF165 binding to NRP-1 seem to be promising candidates as new anti-angiogenic and anti-tumour drugs. Here, we report the design, synthesis, biological evaluation and molecular modelling of the small cyclic peptide, which shows a good inhibitory effect on VEGF165/NRP-1 binding (IC50=0.18μM). The reported compound could be considered as one of the smallest cyclic peptides (MW=510) interfering with VEGF165/NRP-1 binding presented up to now.

Keywords: Angiogenesis; Cyclic peptide; Neuropilin; VEGF(165).

MeSH terms

  • Binding Sites / drug effects
  • Cell Line, Tumor
  • Cell Survival
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Neuropilin-1 / antagonists & inhibitors*
  • Neuropilin-1 / chemistry
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology*
  • Structure-Activity Relationship
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / chemistry

Substances

  • Peptides, Cyclic
  • Vascular Endothelial Growth Factor A
  • Neuropilin-1