Novel Peptides Selected to Bind Vascular Endothelial Growth Factor Target the Receptor-Binding Site

Citations Over TimeTop 10% of 1998 papers

Abstract

Peptides that inhibit binding of vascular endothelial growth factor (VEGF) to its receptors, KDR and Flt-1, have been produced using phage display. Libraries of short disulfide-constrained peptides yielded three distinct classes of peptides that bind to the receptor-binding domain of VEGF with micromolar affinities. The highest affinity peptide was also shown to antagonize VEGF-induced proliferation of primary human umbilical vascular endothelial cells. The peptides bind to a region of VEGF known to contain the contact surface for Flt-1 and the functional determinants for KDR binding. This suggests that the receptor-binding region of VEGF is a binding "hot spot" that is readily targeted by selected peptides and supports earlier assertions that phage-derived peptides frequently target protein-protein interaction sites. Such peptides may lead to the development of pharmacologically useful VEGF antagonists.

Related Papers

• → Phage display: Concept, innovations, applications and future(2010)480 cited
• → Novel peptides binding to the Fc-portion of immunoglobulins obtained from a combinatorial phage display peptide library(1998)20 cited
• Potential GM-CSF Antagonists Selected from a Peptide Phage Display Library.(1999)
• Selection of Ligand from a Heptapeptide Phage Display Library for LPS(2008)
• → Identification of an Indiscriminate Peptide by Phage Display Technology(2020)