Conformational studies on five octasaccharides isolated from chondroitin sulfate using NMR spectroscopy and molecular modeling
Conformational studies on five octasaccharides isolated from chondroitin sulfate using NMR spectroscopy and molecular modeling
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DOI：
10.1021/bi061971f
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发表时间：
2007-02-06
期刊：
影响因子：
2.9
通讯作者：
Kamerling, Johannis P.
中科院分区：
文献类型：
--
作者：
Blanchard, Veronique;Chevalier, Franck;Kamerling, Johannis P.
硫酸软骨素蛋白聚糖（CS-PG）存在于细胞表面和组织的细胞外基质中，参与脊椎动物中枢神经系统的调节。CS部分是由重复的-4)GlcA(β 1-3)GalNAc（β 1- 2）双糖单元组成的，在不同位置部分o -硫酸化。蛋白多糖DSD-1-PG/phosphacan的CS部分中存在二硫化双糖d单元GlcA2S(β 1-3)GalNAc6S，与促进神经突生长有关。单克隆抗体（mAb） 473HD与DSD-1-PG结合，减少神经元刺激，被鲨鱼软骨CS-D抑制。CS-D还被另外两个单克隆抗体MO-225和CS-56识别。利用核磁共振波谱和分子模型对鲨鱼软骨CS-D中分离的五种八糖进行了构象研究。这些八糖对三种单抗具有不同的结合特性。实验和理论方法的结合表明，双糖D中GlcA 2位的硫酸盐基团和双糖C [GlcA(β 1-3)GalNAc6S]和δ C [δ (4,5)HexA(α 1-3)GalNAc6S]中外环负尾的存在对抗体识别很重要。
Chondroitin sulfate proteoglycans (CS-PG) are involved in the regulation of the central nervous system in vertebrates due to their presence on cell surfaces and in the extracellular matrix of tissues. The CS moieties are built up from repeating -4)GlcA(beta 1-3)GalNAc(beta 1- disaccharide units, partly O-sulfated at different positions. The presence of the disulfated disaccharide D-unit, GlcA2S(beta 1-3)GalNAc6S, in the CS moiety of the proteoglycan DSD-1-PG/phosphacan, correlates with neurite outgrowth promotion. The binding of monoclonal antibody (mAb) 473HD to DSD-1-PG, reducing neuronal stimulation, is inhibited by shark cartilage CS-D. CS-D is also recognized by two other mAbs, MO-225 and CS-56. Conformational studies were performed using NMR spectroscopy and molecular modeling on five octasaccharides isolated from shark cartilage CS-D. These octasaccharides present different binding properties toward the three mAbs. The combination of the experimental and theoretical approaches revealed that the sulfate group at position 2 of GlcA in disaccharide D and the presence of an exocyclic negative tail in disaccharides C [GlcA(beta 1-3)GalNAc6S] and Delta C [Delta(4,5)HexA(alpha 1-3)GalNAc6S] are important for antibody recognition.