Department of Radiology, Molecular Imaging Program at Stanford and Bio-X Program, School of Medicine, Stanford University, CA 94305, United States.
Department of Chemistry, Alberta Glycomics Centre, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
Carbohydr Res. 2014 Jan 13;383:1-13. doi: 10.1016/j.carres.2013.10.012. Epub 2013 Nov 1.
A rat monoclonal antibody 9D4 raised against the cell surface N-glycan of the parasite Trichinella spirallis protects rats against further infection. The terminal disaccharide β-d-Tyvp(1→3)β-d-GalNAcp (2) represents the immunodominant portion of the antigenic determinant. Chemical mapping of the antibody binding site by functional group modification employing monodeoxy and mono-O-methyl congeners identified key polar contacts and topography of the bound disaccharide. We report here a comparison of the chemical mapping studies with the antigen topography inferred from saturation transfer difference (STD) NMR experiments. During chemical mapping several congeners of compound 2 showed substantially enhanced binding. Pairing of these functional group modifications to create derivatives 6 and 7 did not show additive free energy gains and STD NMR data point to small variations in mode of binding as a probable cause. Improved syntheses of disaccharides 2-7 are reported.
一种针对寄生虫旋毛虫细胞表面 N-聚糖的鼠单克隆抗体 9D4 可保护大鼠免受进一步感染。末端二糖β-d-Tyvp(1→3)β-d-GalNAcp(2)代表抗原决定簇的免疫显性部分。通过功能基团修饰的化学绘图，使用单脱氧和单-O-甲基类似物来确定结合二糖的关键极性接触和拓扑结构。我们在此报告化学绘图研究与饱和转移差异（STD）NMR 实验推断的抗原拓扑结构的比较。在化学绘图过程中，化合物 2 的几种类似物表现出显著增强的结合。将这些功能基团修饰配对以创建衍生物 6 和 7 并没有显示出附加的自由能增益，并且 STD NMR 数据表明结合模式的微小变化可能是原因。报告了二糖 2-7 的改进合成。
