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

David M. Ornitz, Andrew B. Herr, Marianne Nilsson, Jacob Westman, Carl Magnus Svahn, Gabriel Waksman

Research output: Contribution to journalArticle

265 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)432-436
Number of pages5
JournalScience
Volume268
Issue number5209
DOIs
StatePublished - Jan 1 1995

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