Structural requirements in heparin for binding and activation of FGF-1 and FGF-4 are different from that for FGF-2.

Size- and structure-defined oligosaccharides from heparin, 2-O-desulphated (2-O-DS-) heparin, 6-O-desulphated (6-O-DS-) heparin, carboxy-reduced (CR-) heparin, and carboxyamidomethylsulphonated (AMS-) heparin were utilized in characterizing the structural properties of heparin to specifically bind to basic fibroblast growth factor (FGF-2) and to modulate the mitogenic activity of FGF-2 (Ishihara, M. et al., Glycobiology, 4, 451-458, 1994). The previous results showed that both 2-O-sulphate groups and the negative charge of the carboxy group in iduronate residues are required for specific interaction with FGF-2, but the 6-O-sulphate groups in N-sulphated glucosamine (GlcNS) residues do not influence the interaction with FGF-2. In the present study, the same oligosaccharides were fractionated on a FGF-1- or FGF-4-affinity column, and were assessed as promoters of FGF-1- or FGF-4-induced proliferation of adrenocortical endothelial (ACE) cells and chlorate-treated ACE cells. The present results suggest that the smallest heparin-derived oligosaccharide binding to these growth factors with the highest affinity and promoting their mitogenic activities is a fully N-sulphated decasaccharide enriched in 2-O- and 6-O-sulphated disaccharide units. In contrast to our results with FGF-2, a high content of 6-O-sulphate groups in GlcNS residues is required for specific interaction with FGF-1 and FGF-4.