Importance of 2-O-sulfate groups of uronate residues in heparin for activation of FGF-1 and FGF-2.

Complete drying of heparin with various concentrations of NaOH by lyophilization caused specific 2-O-desulfation to various degrees without detectable depolymerization or other chemical changes. In order to assess the importance of 2-O-sulfate groups in uronate residues to promote FGF-1 and FGF-2 activities, various 2-O-desulfated (2-O-DS-) heparins were quantitatively examined for their effects on FGF-1 and FGF-2-induced proliferation of BALB/c3T3 clone A31 (A31) cells and the chlorate-treated cells. Twenty-seven percent or less loss to the 2-O-sulfate groups had no effect on the ability to activate both FGF-1 and FGF-2, while 44% loss resulted in a significant loss of the ability. Complete loss of the ability was observed in 2-O-DS-heparins with 75% or more 2-O-desulfation. These results suggest that a high content of 2-O-sulfate groups in uronate residues of heparin is required for activation of both FGF-1 and FGF-2.