STRUCTURE OF HEPARIN FRAGMENTS WITH HIGH-AFFINITY FOR LIPOPROTEIN-LIPASE AND INHIBITION OF LIPOPROTEIN-LIPASE BINDING TO ALPHA(2)-MACROGLOBULIN-RECEPTOR LOW-DENSITY-LIPOPROTEIN-RECEPTOR-RELATED PROTEIN BY HEPARIN FRAGMENTS

Heparin-derived deca- and octa-saccharides were subjected to affinity chromatography on lipoprotein lipase-Sepharose and the fractions elute d at high salt concentration were analysed by strong-anion-exchange ch romatography. Two high-affinity deca-saccharides were isolated and the structure determined by one- and two-dimensional H-1-n.m.r. spectrosc opy. The affinities of H-3-labelled low-molecular-mass heparin and siz e-fractionated deca-, octa-, and hexa-saccharides for lipoprotein lipa se immobilized on microtitre plates were determined from saturation cu rves. From competition experiments the affinities of unlabelled hepari ns and pure deca- and hexa-saccharide fragments were determined. The b inding was size- and charge-dependent, but structural dependency was a lso indicated. Thus substitution of a 2-O-sulphated L-iduronic acid wi th D-glucuronic acid was less important than the sulphation pattern of the D-glucosamine residue for affinity for lipoprotein lipase. Hepari n inhibits binding of lipoprotein lipase to (2)-macroglobulin-receptor /low-density-lipoprotein receptor-related protein. The effects of size , charge and structure for this inhibition were studied. The ability o f the heparin fragments to inhibit binding correlated with their affin ity for lipoprotein lipase. This indicates that the inhibition of the binding of lipoprotein lipase to (2)-macroglobulin-receptor/low-densit y-lipoprotein receptor-related protein by heparin is exclusively media ted by binding of heparin to lipoprotein lipase.