Gigli M, Ghiselli G, Torri G, Naggi A, Rizzo V
Farmitalia-Carlo Erba R&D, Nerviano, Milan, Italy.
Biochim Biophys Acta. 1993 Apr 7;1167(2):211-7. doi: 10.1016/0005-2760(93)90164-5.
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.
利用荧光各向异性技术，以荧光素标记的高LDL亲和力肝素片段作为参考进行竞争实验，研究了低密度脂蛋白（LDL）与一系列特性明确的硫酸皮肤素和硫酸软骨素之间的关联。本研究选用了通过分级分离或化学修饰获得的硫酸化程度在很宽范围内变化的糖胺聚糖（GAG）制剂。在先前关于肝素对LDL亲和力的研究中发现链长有显著影响，因此在解离常数的经验校正中考虑了链长因素。校正后发现，硫酸皮肤素、硫酸软骨素以及肝素的解离常数对数与每个二糖单位的硫酸基团数ns之间呈线性关系。然而，在可比的ns值下，主链中含有L-艾杜糖醛酸的硫酸皮肤素和肝素对LDL的亲和力高于仅含有D-葡萄糖醛酸的硫酸软骨素。尽管这些结果证实了GAG与LDL之间存在非特异性的、主要是静电的相互作用，但表明多糖主链对LDL亲和力有调节作用。
