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Drug development targeting fibroblast growth factor receptors (FGFRs) represents an emerging theme in the field of medicinal chemistry. Considering the fact that most of the currently identified FGFR agonists are long chain peptides with limited stability, the discovery of novel non-peptide FGFR ligands is still highly demanded. A linear one-bead-one-compound peptoid (oligomers of N-substituted glycine units) library with a theoretical diversity of 10 6 was designed and synthesized. Microarray-based screening led to the identification of four hit sequences 1 - 4 as FGFR1α ligands, which were further confirmed using both solution-phase and solid-phase binding assays. Western blot results indicated that peptoids 2 - 4 activated FGFR signaling pathways, resulting in increased levels of p-Akt and p-ERK in different cell lines. Our work discovered novel peptoid ligands as FGFR agonists, shedding new light on FGFR-based drug discovery.

Identification of novel peptoid agonists of fibroblast growth factor receptors using microarray-based screening