Gerbst Alexey G, Dmitrenok Andrey S, Ustyuzhanina Nadezhda E, Nifantiev Nikolay E
N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991 Moscow B-334, Russia.
Mar Drugs. 2015 Feb 12;13(2):936-47. doi: 10.3390/md13020936.
Anionic polysaccharides fucosylated chondroitin sulfates (FCS) from holothurian species were shown to affect various biological processes, such as metastasis, angiogenesis, clot formation, thrombosis, inflammation, and some others. To understand the mechanism of FCSs action, knowledge about their spatial arrangement is required. We have started the systematic synthesis, conformational analysis, and study of biological activity of the oligosaccharides related to various fragments of these types of natural polysaccharides. In this communication, five molecules representing distinct structural fragments of chondroitin sulfate have been studied by means of molecular modeling and NMR. These are three disaccharides and two trisaccharides containing fucose and glucuronic acid residues with one sulfate group per each fucose residue or without it. Long-range C-H coupling constants were used for the verification of the theoretical models. The presence of two conformers for both linkage types was revealed. For the Fuc-GlA linkage, the dominant conformer was the same as described previously in a literature as the molecular dynamics (MD) average in a dodechasaccharide FCS fragment representing the backbone chain of the polysaccharide including GalNAc residues. This shows that the studied oligosaccharides, in addition to larger ones, may be considered as reliable models for Quantitative Structure-Activity Relationship (QSAR) studies to reveal pharmacophore fragments of FCS.
来自海参物种的阴离子多糖岩藻糖基化硫酸软骨素（FCS）已被证明会影响各种生物过程，如转移、血管生成、凝血、血栓形成、炎症等。为了了解FCS的作用机制，需要了解它们的空间排列。我们已经开始对与这些类型的天然多糖的各种片段相关的寡糖进行系统合成、构象分析和生物活性研究。在本通讯中，通过分子建模和核磁共振研究了代表硫酸软骨素不同结构片段的五个分子。这些是三个二糖和两个三糖，含有岩藻糖和葡萄糖醛酸残基，每个岩藻糖残基带有一个硫酸基团或不带硫酸基团。远程C-H耦合常数用于验证理论模型。揭示了两种连接类型均存在两种构象体。对于Fuc-GlA连接，主要构象体与先前文献中描述的相同，即代表包括GalNAc残基的多糖主链的十二糖FCS片段中的分子动力学（MD）平均值。这表明，除了较大的寡糖外，所研究的寡糖也可被视为用于定量构效关系（QSAR）研究以揭示FCS药效团片段的可靠模型。
