Peptides Interacting with Growth Factor Receptors Regulating Angiogenesis

Angiogenesis regulation strictly depends on the balance between pro- and anti-angiogenic molecules such as growth factors. Growth factors exert their biological action selectively binding to and activating specific cell membrane receptors which then transfer the message to cell interior triggering specific biochemical pathways ending in the angiogenic response. Molecules able to interfere with the molecular recognition between an angiogenic growth factor and its receptor can modulate the angiogenesis. Peptides are good candidates to develop new lead compounds able to target the growth factor-receptor protein interface for pharmacological applications. In this review we describe peptides targeting the receptors of the pro-angiogenic growth factors Fibroblast Growth Factor, Platelet-Derived Growth Factor and Vascular Endothelial Growth Factor. The biological function and the three-dimensional structure of each growth factor/receptor system are discussed, as well as the molecular interaction between peptides and the receptors. Finally, we highlight the pharmacological and diagnostic applications of these peptides in angiogenesis related diseases.

Keywords: Angiogenesis, anti-angiogenic, cancer, cysteine knot motif, cytokine, endothelial cells, FGF, FGFR, Growth factor, molecular imaging, PDGF, PDGFR, peptide, phage display library, pro-angiogenic, structure-based design, therapeutic angiogenesis, tyrosine kinase receptor, VEGF, VEGFR.