通过 metropolis 蒙特卡罗模拟对与 A 组链球菌细胞壁多糖相对应的寡糖进行构象分析。

Conformational analysis of oligosaccharides corresponding to the cell-wall polysaccharide of the Streptococcus group A by Metropolis Monte Carlo simulations.

作者信息

Stuike-Prill R, Pinto B M

机构信息

Department of Chemistry, Carlsberg Laboratory, Copenhagen, Denmark.

出版信息

Carbohydr Res. 1995 Dec 27;279:59-73. doi: 10.1016/0008-6215(95)00279-0.

DOI:10.1016/0008-6215(95)00279-0

PMID:8593633

Abstract

Metropolis Monte Carlo simulations have been performed on four substructures from the cell-wall polysaccharide antigen of Streptococcus group A to explore the conformational behaviour of these compounds. The compounds examined are the trisaccharide, propyl 3-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-2-O-(alpha-L-rhamnopyranosyl)- alpha-L-rhamnopyranoside, 1, the tetrasaccharide, propyl 3-O-(3-O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-2-O-(alpha-L-rhamnopyranosyl)-alpha-L-rhamnopyranosyl)-alpha-L- rhamnopyranoside, 2, the hexasaccharide, propyl 3-O-(2-O-(3-O-(3-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-alpha-L- rhamnopyranosyl)-alpha-L-rhamnopyranosyl)-3-O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-alpha-L-rhamnopyranosyl)-alpha-L-rhamnopyranoside, 3, and the hexasaccharide, propyl 3-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-2-O-(3-O-(3-O-(2-acetamido-2- deoxy-beta-D-glucopyranosyl)-2-O-(alpha-L-rhamnopyranosyl)-alpha-L- rhamnopyranosyl)-alpha-L-rhamnopyranosyl)-alpha-L-rhamnopyranoside, 4. In general, the conformational flexibility of similar glycosidic linkages in different compounds is comparable. However, in a few cases, small differences in the conformations available to these linkages in different structural environments could be detected. Interestingly, a second conformation found for the beta-D-GlcNAc-(1-->3)-alpha-L-Rha linkage in three of the compounds was not populated in the hexasaccharide 4. Furthermore, a conformational locale of the alpha-L-Rha-(1-->3)-alpha-L-Rha linkage found to be populated in the trisaccharide 1, tetrasaccharide 2, and hexasaccharide 4 is negligibly populated in the hexasaccharide 3. Ensemble averaged proton-proton distances compare favourably with experimental average distances obtained from NMR spectroscopy. The trisaccharide branch point in the hexasaccharides is shown to be a highly defined conformational feature. The same unit has been found to be one of the crucial elements recognized by anti-Group A Streptococcus antibodies, a result that has implications for the design of improved immunodiagnostics and vaccines.

摘要

已对A组链球菌细胞壁多糖抗原的四个亚结构进行了 metropolis 蒙特卡罗模拟，以探究这些化合物的构象行为。所研究的化合物包括三糖，丙基3 - O - (2 - 乙酰氨基 - 2 - 脱氧 - β - D - 吡喃葡萄糖基) - 2 - O - (α - L - 吡喃鼠李糖基) - α - L - 吡喃鼠李糖苷，1；四糖，丙基3 - O - (3 - O - (2 - 乙酰氨基 - 2 - 脱氧 - β - D - 吡喃葡萄糖基) - 2 - O - (α - L - 吡喃鼠李糖基) - α - L - 吡喃鼠李糖基) - α - L - 吡喃鼠李糖苷，2；六糖，丙基3 - O - (2 - O - (3 - O - (3 - O - (2 - 乙酰氨基 - 2 - 脱氧 - β - D - 吡喃葡萄糖基) - α - L - 吡喃鼠李糖基) - α - L - 吡喃鼠李糖基) - 3 - O - (2 - 乙酰氨基 - 2 - 脱氧 - β - D - 吡喃葡萄糖基) - α - L - 吡喃鼠李糖基) - α - L - 吡喃鼠李糖苷，3；以及六糖，丙基3 - O - (2 - 乙酰氨基 - 2 - 脱氧 - β - D - 吡喃葡萄糖基) - 2 - O - (3 - O - (3 - O - (2 - 乙酰氨基 - 2 - 脱氧 - β - D - 吡喃葡萄糖基) - 2 - O - (α - L - 吡喃鼠李糖基) - α - L - 吡喃鼠李糖基) - α - L - 吡喃鼠李糖基) - α - L - 吡喃鼠李糖苷，4。一般来说，不同化合物中相似糖苷键的构象灵活性具有可比性。然而，在少数情况下，可以检测到这些键在不同结构环境中可利用构象的微小差异。有趣的是，在其中三种化合物中发现的β - D - GlcNAc - (1→3) - α - L - Rha键的第二种构象在六糖4中并未出现。此外，在三糖1、四糖2和六糖4中发现的α - L - Rha - (1→3) - α - L - Rha键的一个构象区域在六糖3中的占据程度可忽略不计。系综平均质子 - 质子距离与通过核磁共振光谱获得的实验平均距离相比具有优势。六糖中的三糖分支点显示为一个高度明确的构象特征。已发现相同的单元是抗A组链球菌抗体识别的关键元件之一，这一结果对改进免疫诊断和疫苗的设计具有启示意义。