Olsson U, Camejo G, Olofsson S O, Bondjers G
Wallenberg Laboratory for Cardiovascular Research, Department of Medicine 1, University of Göteborg, Sweden.
Biochim Biophys Acta. 1991 Jul 26;1097(1):37-44. doi: 10.1016/0925-4439(91)90021-z.
The association of low density lipoprotein (LDL) with proteoglycans of the arterial intima, in particular chondroitin 6-sulphate proteoglycans, may contribute to LDL accumulation during atherogenesis. We studied the interactions of apolipoprotein B-100 (apo B-100) peptide segments and model peptides with chondroitin 6-sulphate. The ability of these peptides to inhibit complex formation between LDL and chondroitin 6-sulphate was used as a measurement of the interaction. Results from earlier studies suggest that surface located segments of apo B-100 are responsible for the interaction of LDL with heparin and chondroitin sulphate-rich arterial proteoglycans. Therefore 16 hydrophilic apo B-100 peptides were selected for studies and synthesized with a peptide synthesizer. These synthetic peptides were 7 to 26 amino acids long. Four of the peptides inhibited the association of LDL with chondroitin 6-sulphate, namely apo B segments 4230-4254, 3359-3377, 3145-3157 and 2106-2121. The 3359-3377 segment was the most efficient. A common feature between the interacting peptides was an excess of positively charged side chains and based on these results we synthesized nine model peptides that shared sequence characteristics with the interacting apo B-100 peptides. Five of these: RSGRKRSGK, RSSRKRSGK, RGGRKRGGK, RSRSRSRSR and RGRGRGRGR were shown to block the LDL-chondroitin-6-sulphate association, RSRSRSRSR being the most effective. The results suggest that the optimal association of the peptides with chondroitin 6-sulphate is obtained with a minimal chain length of nine amino acids and a minimum of five positive charges and that flexibility in the binding region is important.
低密度脂蛋白（LDL）与动脉内膜蛋白聚糖，尤其是6-硫酸软骨素蛋白聚糖的结合，可能在动脉粥样硬化形成过程中促使LDL积聚。我们研究了载脂蛋白B-100（apo B-100）肽段及模型肽与6-硫酸软骨素的相互作用。这些肽抑制LDL与6-硫酸软骨素形成复合物的能力被用作相互作用的衡量指标。早期研究结果表明，apo B-100位于表面的肽段负责LDL与富含肝素及硫酸软骨素的动脉蛋白聚糖的相互作用。因此，选择了16个亲水性apo B-100肽段进行研究，并使用肽合成仪进行合成。这些合成肽长度为7至26个氨基酸。其中四个肽抑制了LDL与6-硫酸软骨素的结合，即apo B片段4230 - 4254、3359 - 3377、3145 - 3157和2106 - 2121。3359 - 3377片段最为有效。相互作用肽之间的一个共同特征是带正电荷的侧链过量，基于这些结果，我们合成了九个与相互作用的apo B-100肽具有相同序列特征的模型肽。其中五个：RSGRKRSGK、RSSRKRSGK、RGGRKRGGK、RSRSRSRSR和RGRGRGRGR被证明可阻断LDL与6-硫酸软骨素的结合，RSRSRSRSR最为有效。结果表明，肽与6-硫酸软骨素的最佳结合需要至少九个氨基酸的最短链长和至少五个正电荷，并且结合区域的灵活性很重要。
