CONFORMATION OF GLYCOPEPTIDES & GLYCOPROTEINS

糖肽的构象

• 批准号: 3279439
• 负责人: C. ALLEN BUSH
• 金额: $ 15.72万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE COUNTY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-12-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3279439
• 关键词: ABO(H) blood groups; carbohydrate structure; carbon; computer simulation; conformation; covalent bond; glycopeptides; glycoprotein structure; high performance liquid chromatography; mathematical model; mathematics; molecular energy level; nuclear magnetic resonance spectroscopy; oligosaccharides; stable isotope; temperature

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.

这项研究的目的是增进有关以下方面的知识 控制三维构象的原理 糖蛋白的研究并将分子形状与生物联系起来 通过与已使用的方法类似的方法来实现功能 多肽、蛋白质和多核苷酸。 的构象为 糖蛋白的测定将特别强调它们的 寡糖部分及其糖肽键。 作为 粘蛋白糖蛋白的构象模型，该研究将 使用极地鱼的抗冻糖蛋白以及血液 从卵巢中分离出的 A、B、H 组和 Lewis 活性结构 囊肿粘蛋白。 后者材料包括寡糖 糖醇、糖肽和高分子量多糖 带有 A 型血活性侧链 聚乳糖胺骨架。 质子核磁共振谱，包括质子 模型的核 Overhauser 增强（n.O.e.） 化合物将在构象的帮助下被解释 使用经验势函数进行能量计算。 核磁共振 耦合常数和 n.O.e.将由计算得出 低能分子构象的坐标 与实验数据的比较。 内部运动的证据 低聚糖将寻求分子灵活性 1-6 通过实验对温度依赖性进行联系 构象和NMR弛豫方法。 无柔性分子的构象计算 单一低能量构象将使用统计蒙特卡罗 方法。 对非键合、静电和 与负责的分子力的疏溶剂相互作用 观察到的构象将通过实验确定 非水溶剂中构象的测量 计算方法。