Structure of heparin fragments with high affinity for lipoprotein lipase and inhibition of lipoprotein lipase binding to α2-macroglobulin-receptor/low-density-lipoprotein- receptor-related protein by heparin fragments
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Structure of heparin fragments with high affinity for lipoprotein lipase and inhibition of lipoprotein lipase binding to α2-macroglobulin-receptor/low-density-lipoprotein- receptor-related protein by heparin fragments. / Larnkjær, Anni; Nykjær, A.; Olivecrona, G.; Thøgersen, Henning; Østergaard, P. B.
In: Biochemical Journal, Vol. 307, No. 1, 1995, p. 205-214.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Structure of heparin fragments with high affinity for lipoprotein lipase and inhibition of lipoprotein lipase binding to α2-macroglobulin-receptor/low-density-lipoprotein- receptor-related protein by heparin fragments
AU - Larnkjær, Anni
AU - Nykjær, A.
AU - Olivecrona, G.
AU - Thøgersen, Henning
AU - Østergaard, P. B.
N1 - (Ekstern)
PY - 1995
Y1 - 1995
N2 - Heparin-derived deca- and octa-saccharides were subjected to affinity chromatography on lipoprotein lipase-Sepharose and the fractions eluted at high salt concentration were analysed by strong-anion-exchange chromatography. Two high-affinity deca-saccharides were isolated and the structure determined by one- and two-dimensional 1H-n.m.r. spectroscopy. The affinities of 3H-labelled low-molecular-mass heparin and size-fractionated deca-, octa-, and hexa-saccharides for lipoprotein lipase immobilized on microtitre plates were determined from saturation curves. From competition experiments the affinities of unlabelled heparins and pure deca- and hexa-saccharide fragments were determined. The binding was size- and charge-dependent, but structural dependency was also indicated. Thus substitution of a 2-O-sulphated L-iduronic acid with D-glucuronic acid was less important than the sulphation pattern of the D-glucosamine residue for affinity for lipoprotein lipase. Heparin inhibits binding of lipoprotein lipase to α2-macroglobulin-receptor/low-density-lipoprotein receptor-related protein. The effects of size, charge and structure for this inhibition were studied. The ability of the heparin fragments to inhibit binding correlated with their affinity for lipoprotein lipase. This indicates that the inhibition of the binding of lipoprotein lipase to α2-macroglobulin-receptor/low-density-lipoprotein receptor-related protein by heparin is exclusively mediated by binding of heparin to lipoprotein lipase.
AB - Heparin-derived deca- and octa-saccharides were subjected to affinity chromatography on lipoprotein lipase-Sepharose and the fractions eluted at high salt concentration were analysed by strong-anion-exchange chromatography. Two high-affinity deca-saccharides were isolated and the structure determined by one- and two-dimensional 1H-n.m.r. spectroscopy. The affinities of 3H-labelled low-molecular-mass heparin and size-fractionated deca-, octa-, and hexa-saccharides for lipoprotein lipase immobilized on microtitre plates were determined from saturation curves. From competition experiments the affinities of unlabelled heparins and pure deca- and hexa-saccharide fragments were determined. The binding was size- and charge-dependent, but structural dependency was also indicated. Thus substitution of a 2-O-sulphated L-iduronic acid with D-glucuronic acid was less important than the sulphation pattern of the D-glucosamine residue for affinity for lipoprotein lipase. Heparin inhibits binding of lipoprotein lipase to α2-macroglobulin-receptor/low-density-lipoprotein receptor-related protein. The effects of size, charge and structure for this inhibition were studied. The ability of the heparin fragments to inhibit binding correlated with their affinity for lipoprotein lipase. This indicates that the inhibition of the binding of lipoprotein lipase to α2-macroglobulin-receptor/low-density-lipoprotein receptor-related protein by heparin is exclusively mediated by binding of heparin to lipoprotein lipase.
UR - http://www.scopus.com/inward/record.url?scp=0028902050&partnerID=8YFLogxK
U2 - 10.1042/bj3070205
DO - 10.1042/bj3070205
M3 - Journal article
C2 - 7717977
AN - SCOPUS:0028902050
VL - 307
SP - 205
EP - 214
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
IS - 1
ER -
ID: 249248164