Synthesis and Fibroblast Growth Factor Binding of Oligosaccharides Related to Heparin and Heparan Sulphate

A series of six disaccharides, α-l-IdoA-(l →4)-α-d-GlcNAc-l→OMe, α-l-IdoA-(l →4)-α-d-GlcNSO3-l →OMe, β-d-GlcA-(l →4)-α-d-GlcNAc-l →OMe, β-d-GlcA-(l→4)-α-d-GlcNSO3-l→OMe, α-d-GlcNAc-(l →4)-β-d-GlcA-l →OMe, β-d-GlcNAc-(l→4)-β-d-GlcA-l→OMe, and two trisaccharide, β-d-GlcA-(1 y4)-α-d-GlcNAc-(1 →4)-β-d-GlcA-l →OMe, α-l-IdoA-(l →4)-α-d-GIcNSO3-(1 →4)-β-d-GlcA-l →OMe was prepared and screened for biological activity in vitro. The oligosaccharides were tested, together with a previously synthesized trisaccharide, α-l-IdoA-(l →4)-α-d-GlcNAc-(l →4)-β-d-GlcA-l →OMe, and three tetrasaccharides, α-l-IdoA-(l →4)-α-d-GlcNAc-(l →4)-β-d-GlcA-(l →3)-β-d-Gal-l →OMe, β-d-GlcA-(l →3)-β-d-Gal-(l →3)-α-d-Gal-(1→3)-2-PO3-β-d-Xyl-l →OMe, β-d-GlcA-(1 →3)-β-d-Gal-(1 →3)-β-d-Gal-(1→3)-β-d-Xyl-l →OMe, for competitive binding to acidic and basic fibroblast growth factor in an assay using 125I labelled heparin. It was found that the non-sulphated trisaccharides, α-l-IdoA-(l →4)-α-d-GlcNAc-(l →4)-β-d-GlcA-l →OMe and β-d-GlcA-(l →4)-α-d-GlcNAc-(l →4)-β-d-GlcA-l- →OMe, and two of the disaccharides can bind to acidic as well as basic FGF.