Basic fibroblast growth factor (bFGF) is a potent heparin binding growth factor that promotes proliferation, migration and differentiation of mesenchymal and neuro ectodermal cells. It exerts its functions by binding to bFGF receptor on cell membranes1. bFGF inhibitory peptides are short peptides that inhibit bFGF receptor binding and its biological function1.
bFGF inhibitory peptides were isolated from a phage epitope library using monoclonal antibodies raised against human recombinant bFGF. These monoclonal antibodies were found to efficiently block bFGF binding to its receptors1.
So far three bFGF inhibitory peptides have been characterized: bFGF inhibitory peptide, bFGF 119-126 and bFGF inhibitory peptide II1.
The inhibitory peptides share a consensus sequence Pro-(Pro/Ser)-Gly-His-(Tyr/Phe)-Lys that corresponds to bFGF sequences at 13-18 and 120-1251.
Mode of action
bFGF 119-126 inhibits the dimerization and binding of bFGF receptors1. bFGF inhibitory peptide blocks the binding of bFGF-induced proliferation of vascular endothelial cells2,3. bFGF inhibitory peptide II has conformational similarity to the putative receptor binding domain of bFGF and hence blocks bFGF binding to its receptor4.
Inhibition or de-regulation of bFGF leads to pathological conditions involving angiogenesis and tumor growth2. bFGF inhibitory peptide II suppresses the proliferation of human glioma cells and is a potential new product for the treatment of malignant glioma4.
1. Avener Y, David A, Michal S, Janet L. G, Yehudit H, Shmuel C, David G, and Ephraim KK (1993). Isolation of peptides that inhibit binding of basic fibroblast growth factor to its receptor from a random phage-epitope library. Proc. Natl. Acad. Sci. USA, 90,10643-10647.
2. Luo J and Miller MW (1996). Ethanol inhibits bFGF-mediated proliferation of C6 glioma cells. J. Neurochem., 67, 1448-1456.
3. Torsten G, Hae YS, Gerald AM, and Ulrich P (2002). Shear Stress-induced Release of Basic Fibroblast Growth Factor from Endothelial Cells Is Mediated by Matrix Interaction via Integrin aVß3. J. Biol. Chem., 277, 23453 – 23458.
4. Gloe T, Sohn HY, Gerald AM, and Ulrich P (2002). Shear-stress induced release of bFGF from endothelial cells is mediated by matrix interaction via integrin alpha V beta 3. J. Biol. Chem., 277, 23453.
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