High-affinity FGFR2 Binding Peptides Derived from the Native Epitope of the KGF Ligand
The fibroblast growth factor receptors (FGFRs) are cell surface tyrosine kinase receptors that are implicated in numerous processes during cell growth and development. KGF (keratinocyte growth factor, FGF-7) is a member of the FGF family that binds the FGF receptor splice variant: FGF-R2(IIIb), i.e., KGF-R. KGF mediates proliferation of epithelial cells and has potential for treatment of oral mucositis, venous ulcers and ulcerative colitis. A series of high affinity peptides based on the native sequence of the RTQ loop (residues 65-80) of KGF were synthesized and tested for their ability to inhibit the binding of KGF to its receptor, KGFR (FGFR2IIIb). The structures of those synthetic peptides were optimized primarily by varying their length at the N- and C-termini, mutating some of the key residues at the N- and C-termini, and introducing an intramolecular disulfide constraint with various loop sizes. In addition, the position of the native RTQ epitope was varied within...
KeywordsUlcerative Colitis Synthetic Peptide Fibroblast Growth Factor Receptor Oral Mucositis Keratinocyte Growth Factor
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