PUBLICATION
Fibroblast Growth Factor 2-antagonist Activity of a Long-Pentraxin 3-derived Antiangiogenic Pentapeptide
- Authors
- Leali, D., Bianchi, R., Bugatti, A., Nicoli, S., Mitola, S., Ragona, L., Tomaselli, S., Gallo, G., Catello, S., Rivieccio, V., Zetta, L., and Presta, M.
- ID
- ZDB-PUB-090727-14
- Date
- 2010
- Source
- Journal of Cellular and Molecular Medicine 14(8): 2109-2121 (Journal)
- Registered Authors
- Presta, Marco
- Keywords
- angiogenesis, FGF, pentraxin, BIAcore, NMR, receptors, heparan sulfate, zebrafish, chorioallantoic membrane, embryo, tumor
- MeSH Terms
-
- Amino Acid Sequence
- Angiogenesis Inhibitors/pharmacology
- Animals
- Binding Sites/genetics
- C-Reactive Protein/chemistry*
- C-Reactive Protein/metabolism
- CHO Cells
- Cell Proliferation/drug effects
- Cell Transplantation/methods
- Chick Embryo
- Cricetinae
- Cricetulus
- Endothelial Cells/metabolism
- Endothelial Cells/transplantation
- Female
- Fibroblast Growth Factor 2/antagonists & inhibitors*
- Fibroblast Growth Factor 2/genetics
- Fibroblast Growth Factor 2/metabolism
- Humans
- Magnetic Resonance Spectroscopy
- Male
- Neovascularization, Physiologic/drug effects
- Oligopeptides/metabolism
- Oligopeptides/pharmacology*
- Protein Binding/drug effects
- Receptor, Fibroblast Growth Factor, Type 1/metabolism
- Serum Amyloid P-Component/chemistry*
- Serum Amyloid P-Component/metabolism
- Transplantation, Heterologous
- Zebrafish
- PubMed
- 19627396 Full text @ J. Cell. Mol. Med.
Citation
Leali, D., Bianchi, R., Bugatti, A., Nicoli, S., Mitola, S., Ragona, L., Tomaselli, S., Gallo, G., Catello, S., Rivieccio, V., Zetta, L., and Presta, M. (2010) Fibroblast Growth Factor 2-antagonist Activity of a Long-Pentraxin 3-derived Antiangiogenic Pentapeptide. Journal of Cellular and Molecular Medicine. 14(8):2109-2121.
Abstract
Fibroblast growth factor-2 (FGF2) plays a major role in angiogenesis. The pattern recognition receptor long-pentraxin 3 (PTX3) inhibits the angiogenic activity of FGF2. To identify novel FGF2-antagonistic peptide(s), four acetylated (Ac) synthetic peptides overlapping the FGF2-binding region PTX3-(97-110) were assessed for their FGF2-binding capacity. Among them, the shortest pentapeptide Ac-ARPCA-NH(2) [PTX3-(100-104)] inhibits the interaction of FGF2 with PTX3 immobilized to a BIAcore sensorchip and suppresses FGF2-dependent proliferation in endothelial cells, without affecting the activity of unrelated mitogens. Also, Ac-ARPCA-NH(2) inhibits angiogenesis triggered by FGF2 or by tumorigenic FGF2-overexpressing murine endothelial cells in chick and zebrafish embryos, respectively. Accordingly, the peptide hampers the binding of FGF2 to Chinese Hamster Ovary cells overexpressing the tyrosine-kinase FGF receptor-1 (FGFR1) and to recombinant FGFR1 immobilized to a BIAcore sensorchip without affecting heparin interaction. In all the assays the mutated Ac-ARPSA-NH(2) peptide was ineffective. In keeping with the observation that hydrophobic interactions dominate the interface between FGF2 and the FGF-binding domain of the Ig-like loop D2 of FGFR1, amino acid substitutions in Ac-ARPCA-NH(2) and Saturation Transfer Difference-NMR analysis of its mode of interaction with FGF2 implicate the hydrophobic methyl groups of the pentapeptide in FGF2 binding. These results will provide the basis for the design of novel PTX3-derived anti-angiogenic FGF2 antagonists.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping