ISOLATION OF HEPARIN-DERIVED OLIGOSACCHARIDES CONTAINING 2-O-SULFATEDHEXURONIC ACIDS, BY LIPOPROTEIN-LIPASE AFFINITY-CHROMATOGRAPHY

Oligosaccharides (hexa to dodeca) terminating with [H-3]2,5-anhydroman nitol (AMan(R)) were isolated from heparin by partial cleavage with ni trous acid at low pH (pH 1.5) followed by gel filtration and reduction with [H-3]NaBH4. They were subsequently chromatographed on a lipoprot ein lipase (LpL)-Sepharose column. High- and low-affinity oligosacchar ides for LpL were isolated and characterized. Disaccharide analysis re vealed the presence of (IdceA(2-SO4) --> AMan(R)6-SO4) and (IdceA(2-SO 4) --> AMan(R)) as the major disaccharide products after low pH nitrou s acid treatment. The oligosaccharides are, therefore, enriched in Idc eA(2-SO4)-(GlcNSO(4) +/- 6-SO4) sequences. Furthermore, they are found to be composed of 2-O-sulfated hexuronic acid-containing sequences, s tructural features, characteristic of heparin and heparan sulfate olig osaccharies with potential antiproliferative activities. These oligosa ccharides may have the potential as lipase-releasing agents from endot helial and adipocyte surfaces.