A comparative study of low-density lipoprotein interaction with glycosaminoglycans.
The association between low-density lipoprotein (LDL) and a series of well characterized dermatan and chondroitin sulfates has been investigated by means of the fluorescence anisotropy technique with competition experiments using a fluorescein-labeled high LDL-affinity heparin fraction as a reference. Preparations of glycosaminoglycan (GAG) with sulfation degrees varying over a wide range, as obtained by fractionation or by chemical modification, were chosen for this study. The influence of chain length, which had been found sizeable in a former study of heparin affinity for LDL, was taken into account with an empirical correction of dissociation constants. After this correction, a linear relationship was found between the logarithm of dissociation constants and the number of sulfate groups per disaccharide unit, ns, both for dermatan and chondroitin sulfates, and for heparins. At comparable ns values, however, dermatan sulfates and heparins, which contain L-iduronic acid in their backbone, show higher LDL-affinity than chondroitin sulfates, which contain only D-glucuronic acid. Though confirming a non-specific, predominantly electrostatic interaction between GAGs and LDL, these results indicate modulation of LDL affinity by the polysaccharide backbone.
Gigli
M
M
Farmitalia-Carlo Erba R&D, Nerviano, Milan, Italy.
Ghiselli
G
G
Torri
G
G
Naggi
A
A
Rizzo
V
V
D001665:Binding Sites; D001667:Binding, Competitive; D002240:Carbohydrate Sequence; D002809:Chondroitin Sulfates / Q000378:metabolism; D003871:Dermatan Sulfate / Q000378:metabolism; D005454:Fluorescence Polarization; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D008433:Mathematics; D008969:Molecular Sequence Data; D008970:Molecular Weight
D006025:Glycosaminoglycans; D008077:Lipoproteins, LDL; D003871:Dermatan Sulfate; D006493:Heparin; D002809:Chondroitin Sulfates