CHARACTERIZATION OF HEPARAN-SULFATE OLIGOSACCHARIDES THAT BIND TO HEPATOCYTE GROWTH-FACTOR

Proteoglycans from rat liver had the ability to bind hepatocyte growth factor (HGF). Digestion of the proteoglycans with heparitinase result ed in the complete loss of the activity, while the digestion with chon droitinase ABC had no effect. Heparan sulfate (HS)-conjugated gel also bound HGF, and the binding was competitively inhibited by heparin and bovine liver HS, but not by Engelbreth-Holm-Swarm sarcoma HS, pig aor ta HS, or other glycosaminoglycans, suggesting the specific structural domain in HS for the binding of HGF. Among limited digests with hepar itinase I of bovine liver HS, octasaccharide is the minimal size to bi nd I-IGF. Comparison of the disaccharide unit compositions revealed a marked difference in IdoA(2SO(4))-GlcNSO(3)(GSO(4)) unit between the b ound and unbound octasaccharides. The contents of this disaccharide un it were calculated to be 2 mol/mol for the bound octasaccharide but 1 mol/mol for the unbound one. Considering both the substrate specificit y and properties of heparitinase I, the above results suggest that the bound octasaccharide should contain two units of IdoA(2SO(4))-GlcNSO( 3)(GSO(4)) contiguously or alternately in the vicinity of the reducing end. The bound decasaccharide was more than 20 times as active as the unbound one with regard to the ability to release HGF bound to rat Li ver HS proteoglycan. The ability was comparable to the one-fourth of t hat of heparin.