title: Potentiation of fibroblast growth factor activity by synthetic heparin oligosaccharide glycodendrimers.
abstract: Heparin is a highly sulfated polysaccharide that regulates a variety of cellular processes by interaction with a host of proteins. We report the preparation of synthetic heparin oligosaccharide glycodendrimers and their use as heparin mimetics to regulate heparin-protein interactions. The multivalent display of sugar epitopes mimics the naturally occurring glycans found on cell surfaces and enhances their binding capacity. Binding of the heparin dendrimers to basic fibroblast growth factor (FGF-2) was analyzed using heparin microarray experiments and surface plasmon resonance measurements on gold chips. Heparin-coated dendrimers bind FGF-2 significantly more effectively than monovalent heparin oligosaccharides. Dendrimer 1, which displays multiple copies of the sulfated hexasaccharide (GlcNSO(3)[6-OSO(3)]-IdoA[2-OSO(3)])3, was employed to promote FGF-2-mediated mitogen-activated kinase activation, demonstrating the utility of glycodendrimers to modulate heparin-protein interactions.
authors: Laboratory of Organic Chemistry, Swiss Federal Institute of Technology (ETH) Zürich, 8093 Zürich, Switzerland.
authors: Jose L
authors: JL
authors: de Paz
authors: Christian
authors: C
authors: Noti
authors: Friederike
authors: F
authors: Böhm
authors: Sabine
authors: S
authors: Werner
authors: Peter H
authors: PH
authors: Seeberger
mesh_terms: D050091:Dendrimers / Q000494:pharmacology*; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D009844:Oligosaccharides / Q000494:pharmacology*; D020349:Surface Plasmon Resonance
chemical_list: D050091:Dendrimers; D009844:Oligosaccharides; D016222:Fibroblast Growth Factor 2; D006493:Heparin