Selection of peptide ligands binding to fibroblast growth factor receptor 1.
Inappropriate expression of fibroblast growth factors (FGFs) or activation of FGF receptors (FGFRs) could contribute to several human angiogenic pathologies. In an attempt to design antagonists of FGF, we developed a screening procedure for identifying peptide ligands binding to FGFR1. To retain the natural conformation of FGFR1 during screening, we expressed recombinant FGFR1 on the surface of Sf9 insect cells. A 6-mer phage display peptide library was then screened on the cell surface and a group of hydrophobic peptide sequences were identified. Further experiments demonstrated that the phages displaying these sequences can specifically bind to FGFR1. The docking analysis suggests that the peptide ValTyrMetSerProPhe can specifically bind to the hydrophobic surface of FGFR1. The synthetic peptide Ac-ValTyrMetSerProPhe-NH2 can inhibit mitogenic activity of aFGF and has the potential to become a therapeutic agent as an aFGF antagonist.
Fan
Hongkuan
H
College of Life Science, Jilin University, Changchun, People's Republic of China.
Duan
Yanfen
Y
Zhou
Hui
H
Li
Wei
W
Li
Fei
F
Guo
Lili
L
Roeske
Roger W
RW
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001435:Bacteriophages / Q000235:genetics / Q000378:metabolism; D016367:Baculoviridae / Q000235:genetics; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D004926:Escherichia coli / Q000235:genetics; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D018411:Spodoptera / Q000166:cytology
D000911:Antibodies, Monoclonal; D008024:Ligands; D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D016220:Fibroblast Growth Factor 1; C496348:FGFR1 protein, human; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1