Targeting angiogenesis: Structural characterization and biological properties of a de novo engineered VEGF mimicking peptide.

Modulating angiogenesis is an attractive goal because many pathol. conditions depend on the growth of new vessels. Angiogenesis is mainly regulated by the VEGF, a mitogen specific for endothelial cells. In the last years, many efforts have been pursued to modulate the angiogenic response targeting VEGF and its receptors. Based on the x-ray structure of VEGF bound to the receptor, the authors designed a peptide, QK, reproducing a region of the VEGF binding interface: the helix region 17-25. NMR conformation anal. of QK revealed that it adopts a helical conformation in water, whereas the peptide corresponding to the a-helix region of VEGF, VEGF15, is unstructured. Biol. assays in vitro and on bovine aorta endothelial cells suggested that QK binds to the VEGF receptors and competes with VEGF. VEGF15 did not bind to the receptors indicating that the helical structure is necessary for the biol. activity. Furthermore, QK induced endothelial cells proliferation, activated cell signaling dependent on VEGF, and increased the VEGF biol. response. QK promoted capillary formation and organization in an in vitro assay on matrigel. These results suggested that the helix region 17-25 of VEGF is involved in VEGF receptor activation. The peptide designed to resemble this region shares numerous biol. properties of VEGF, thus suggesting that this region is of potential interest for biomedical applications, and mols. mimicking it could be attractive for therapeutic and diagnostic applications.