Selection of peptide ligands that bind to acid fibroblast growth factor.
Acid fibroblast growth factor (aFGF) binds to its cell-surface receptors in a heparin-dependent manner. In an attempt to define the aFGF recognition site on fibroblast growth factor receptor 1 (FGFR1), we developed a screening strategy for identifying FGF ligands that bind to the receptor-binding region of FGF. To retain the natural conformation of aFGF during screening, we used biotinylated heparin to immobilize aFGF on a streptavidin-coated dish. A 15-mer phage display peptide library was then screened in the dish and a group of related peptide sequences was identified. These peptide sequences contain two conserved motifs, SSG and VPS, corresponding to two protein sequences of the immunoglobulin-like (Ig-like) domain II of FGFR1 at amino acids 180-182 and 221-223 (CPSSG-VPSDKGNYTC). Further experiments demonstrate that the phage displaying these sequences can specifically bind to aFGF and that the synthesized peptide corresponding in sequence can inhibit mitogenic activity of aFGF. These sequences may thus constitute part of the aFGF-binding region on FGFR1, and the synthesized peptide has the potential to become a therapeutic agent as an aFGF antagonist.
Fan
H
H
College of Life Science, Jilin University Changchun, PR China.
Liu
Y
Y
Zhou
H
H
Wang
L
L
Li
W
W
Guo
L
L
Roeske
R W
RW
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
D008024:Ligands; 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