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Christine Piossek, Karl-Heinz Thierauch, Jens Schneider-Mergener, Rudolf Volkmer-Engert, Martin F. Bachmann, Thomas Korff, Hellmut G. Augustin, Lothar Germeroth
Potent inhibition of angiogenesis by D,L-peptides derived from vascular endothelial growth factor receptor 2
Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells and plays a central role in angiogenesis and vasculogenesis. Therefore, VEGF and its receptors VEGFR-1 and VEGFR-2 are prime targets for anti-angiogenic intervention which is thought to be one of the most promising approaches in cancer therapy. Recently, we have discovered a VEGFR-2-derived peptide (247RTELNVGIDFNWEYP261) representing a potential binding site to VEGF. Using the spot synthesis technique, systematic D-amino acid substitutional analyses of this peptide were conducted and the resulting D,L-peptides inhibit VEGF binding to VEGFR-2 at half maximal concentration of 30 nM. The serum-stable D,L-peptides further inhibited autophosphorylation of the VEGFR-2 at nanomolar concentrations. Testing of the peptides in a spheroid-based angiogenesis assay demonstrated a potent anti-angiogenic effect in vitro. The rational design of potent and stable anti-angiogenic peptide inhibitors from their parent receptors provides a feasible route to develop novel leads for anti-angiogenic medicines.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 90, 09/2003
Pages: 501 - 510