FGF BINDING AND FGF RECEPTOR ACTIVATION BY SYNTHETIC HEPARAN-DERIVED DISACCHARIDES AND TRISACCHARIDES

Fibroblast growth factors (FGFs) require a polysaccharide cofactor, he parin or heparan sulfate (HS), for receptor binding and activation. To probe the molecular mechanism by which heparin or HS (heparin/HS) act ivates FGF, small nonsulfated oligosaccharides found within heparin/HS were assayed for activity, These synthetic and isomerically pure comp ounds can activate the FGF signaling pathway. The crystal structures o f complexes between FGF and these heparin/HS oligosaccharides reveal s everal binding sites on FGF and constrain possible mechanisms by which heparin/HS can activate the FGF receptor. These studies establish a f ramework for the molecular design of compounds capable of modulating F GF activity.