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.
Ishihara
M
M
Glycomed Inc., Alameda, CA 94501, USA.
D001665:Binding Sites; D002240:Carbohydrate Sequence; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006493:Heparin / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D008024:Ligands; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009844:Oligosaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D013431:Sulfates / Q000737:chemistry
D051519:Fibroblast Growth Factor 4; D008024:Ligands; D009844:Oligosaccharides; D011518:Proto-Oncogene Proteins; D013431:Sulfates; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D005346:Fibroblast Growth Factors; D006493:Heparin