Conformational latitude - activity relationship of KPPR tetrapeptide analogues toward their ability to inhibit binding of vascular endothelial growth factor 165 to neuropilin-1

J Pept Sci. 2017 Jun;23(6):445-454. doi: 10.1002/psc.3009. Epub 2017 May 3.

Abstract

Neuropilin-1 has been found to be overexpressed in several kinds of malignant tumors, and it is postulated that its interaction with the vascular endothelial growth factor 165 leads to progression of tumor vascularization and growth. Several analogues (KxxR) with various conformational latitudes have been synthesized and found as inhibitors of NRP-1. Detailed insight provided by molecular dynamics simulation allowed forming a clear relationship between flexibility of xx part of the molecule and its inhibitory activity.

Keywords: VEGF165; conformational latitude; inhibitors of NRP-1; molecular dynamics.

MeSH terms

  • Binding Sites / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Models, Molecular
  • Neuropilin-1 / antagonists & inhibitors*
  • Neuropilin-1 / chemistry
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Protein Conformation
  • Structure-Activity Relationship
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / chemistry

Substances

  • Oligopeptides
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Neuropilin-1