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Science. 1995 Apr 21;268(5209):432-6.

FGF binding and FGF receptor activation by synthetic heparan-derived di- and trisaccharides.

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  • 1Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, MO 63110, USA.


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

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