Design and synthesis of C-terminal modified cyclic peptides as VEGFR1 antagonists

Molecules. 2014 Sep 26;19(10):15391-407. doi: 10.3390/molecules191015391.

Abstract

Previously designed cyclic peptide antagonist c[YYDEGLEE]-NH2 disrupts the interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFRs). It represents a promising tool in the fight against cancer and age-related macular degeneration. We described in this paper the optimization of the lead peptide by C-terminal modification. A new strategy for the synthesis of cyclic peptides is developed, improving the cyclisation efficiency. At 100 µM, several new peptides with an aromatic group flexibly linked at C-terminal end showed significantly increased receptor binding affinities in competition ELISA test. The most active peptide carrying a coumarin group may be a useful tool in anti-angiogenic biological studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology
  • Binding Sites
  • Catalytic Domain
  • Drug Design*
  • Models, Molecular
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / pharmacology*
  • Protein Binding / drug effects
  • Protein Conformation
  • Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-1 / chemistry*
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism
  • Vascular Endothelial Growth Factors / metabolism

Substances

  • Angiogenesis Inhibitors
  • Peptides, Cyclic
  • Vascular Endothelial Growth Factors
  • Vascular Endothelial Growth Factor Receptor-1