CONFORMATION OF GLYCOPEPTIDES & GLYCOPROTEINS

这项研究的目的是为了增进对 控制三维构象的原理 并将分子形状与生物学联系起来 功能的方法类似于那些已被用于 多肽、蛋白质和多核苷酸。 的构象 糖蛋白将被确定，特别强调其 寡糖部分和它们的糖肽键。 作为 粘蛋白糖蛋白的构象模型，该研究将 利用极地鱼类的抗冻糖蛋白和血液 A、B、H和刘易斯活性结构 囊肿粘蛋白。 后一种材料包括低聚糖 糖醇、糖肽和高分子量多糖 A型血活性侧链连接到 聚乳糖胺主链。 质子NMR光谱，包括质子 核奥弗豪泽增强（n.O.e.）为模型 化合物将被解释与构象的帮助下， 能量计算与经验势函数。 NMR 耦合常数和n.O.e.将根据 低能量分子构象的坐标， 与实验数据比较。 内部运动的证据 和分子的灵活性将寻求低聚糖， 1-6联系的温度依赖性的实验 构象和核磁共振弛豫方法。 不含碳原子的柔性分子的构象计算 单一低能构象将使用统计蒙特卡罗 方法. 非键合、静电和 疏溶剂相互作用的分子力负责 所观察到的构象将通过实验确定， 在非水溶剂中的构象的测量， 计算方法

The purpose of this research is to advance knowledge concerning the principles which govern the three dimensional conformations of glycoproteins and to relate molecular shape to biological function by methods similar to those which have been used for polypeptides, proteins and polynucleotides. The conformations of glycoproteins will be determined with special emphasis on their oligosaccharide moieties and their glycopeptide linkage. As conformational models for mucin glycoproteins, the research will use the antifreeze glycoprotein of polar fish as well as blood group A, B, H and Lewis active structures isolated from ovarian cyst mucins. The latter materials include oligosaccharide alditols, glycopeptides and a high molecular weight polysaccharide with blood group A active side chains attached to a polylactosamine backbone. Proton NMR spectra, including proton nuclear Overhauser enhancements (n.O.e.) for the model compounds will be interpreted with the help of conformational energy calculations with empirical potential functions. NMR coupling constants and n.O.e. will be calculated from the coordinates of the low energy molecular conformations for comparison with experimental data. Evidence for internal motion and molecular flexibility will be sought for oligosaccharides with 1-6 linkages by experiments on the temperature dependence of the conformation and by NMR relaxation methods. Conformational calculations for flexible molecules having no single low energy conformation will use statistical Monte Carlo methods. The contributions on non-bonded, electrostatic and solvophobic interactions to the molecular forces responsible for the observed conformations will be determined by experimental measurements of the conformation in nonaqueous solvents and by computational methods.