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-methyltrimethylsilyl-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-2 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.
Ishihara
M
M
Seikagaku Corporation, Tokyo Research Institute.
Takano
R
R
Kanda
T
T
Hayashi
K
K
Hara
S
S
Kikuchi
H
H
Yoshida
K
K
D000818:Animals; D002240:Carbohydrate Sequence; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D004187:Disaccharides / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005944:Glucosamine; D006493:Heparin / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D008969:Molecular Sequence Data; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D013464:Sulfuric Acids; D014162:Transfection
D004187:Disaccharides; D011994:Recombinant Proteins; D013464:Sulfuric Acids; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D006493:Heparin; D005944:Glucosamine