IMPORTANCE OF 6-O-SULFATE GROUPS OF GLUCOSAMINE RESIDUES IN HEPARIN FOR ACTIVATION OF FGF-1 AND FGF-2

Treatment of the pyridinium salts of heparin with N-metlhyltrimethylsilyl-trifluoroacetamide (MTSTFA) in pyridine for 2 h at various temperatures caused specific 6-O-desulfations from trisulfated disaccharide units to various degrees without detectable depolymerization or other chemical changes, In order to assess the importance of 6-O-sulfate groups in N-sulfated glucosamine (GlcNS) residues to promote FGF-1 and FGF-S activities, various 6-O-desulfated (6-O-DS-) heparins were quantitatively examined for activity as enhancers or inhibitors of specific FGF-1- and FGF-2-induced proliferation of BALB/c3T3 clone A31 (A31) cells and the chlorate-treated cells. The present results suggested that a high content of 6-O-sulfate groups in GlcNS residues was required for activation of FGF-1, but not FGF-2, However, complete 6-O-desulfation of trisulfated disaccharide units in heparin resulted in loss of the ability to activate FGF-2, although the desulfated product bound strongly to FGF-2.