N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) inhibits the angiogenic activity of heparin-binding growth factors.

摘要: The peptides N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) and BOC-Met-Leu-Phe (BOC1) are widely used antagonists of formyl peptide receptors (FPRs), BOC2 acting as an FPR1/FPR2 antagonist whereas BOC1 inhibits FPR1 only. Extensive investigations have been performed by using these FPR a tool to assess the role FPRs in physiological pathological conditions. Based on previous observations from our laboratory, we assessed possibility that may exert also direct inhibitory effect angiogenic activity vascular endothelial growth factor-A (VEGF-A). Our data demonstrate BOC2, but not BOC1, heparin-binding VEGF-A165 with no non-heparin-binding VEGF-A121 isoform. Endothelial cell-based bioassays, surface plasmon resonance analysis, computer modeling indicate interact domain VEGF-A165, thus competing for heparin interaction preventing binding tyrosine kinase receptor VEGFR2, its phosphorylation downstream signaling. In addition, variety factors heparin, including fibroblast factor 2 (FGF2) whose is blocked compound. Accordingly, suppresses potential human tumor cell lines co-express VEGF-A FGF2. Thus, appears act novel multi-heparin-binding antagonist. These findings caution about interpretation FPR-focusing experimental obtained this compound set basis design BOC2-derived, independent multi-target angiogenesis inhibitors.