CONFORMATION OF GLYCOPEPTIDES AND GLYCOPROTEINS

糖肽和糖蛋白的构象

• 批准号: 3279431
• 负责人: C. ALLEN BUSH
• 金额: $ 14.41万
• 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/3279431
• 关键词: ABO(H) blood groups; carbohydrate structure; computer simulation; conformation; covalent bond; glycopeptides; glycoprotein structure; high performance liquid chromatography; mathematical model; mathematics; molecular energy level; nuclear magnetic resonance spectroscopy; oligosaccharides; 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对以下方面的认识 支配三维构象的原理 并将分子形状与生物学联系起来 函数所使用的方法与用于 多肽、蛋白质和多核苷酸。的构象 糖蛋白的测定将特别强调它们的 低聚糖部分及其糖肽连接。AS 粘蛋白糖蛋白的构象模型，研究将 用北极鱼的抗冻糖蛋白和血液 从卵巢分离的A、B、H和Lewis活性结构 囊肿性粘液。后一种物质包括寡糖 糖醇、糖肽和一种高分子量多糖 A型血型的活性侧链连接到 聚乳糖胺主链。质子核磁共振谱，包括质子 Overhauser的核增强功能(不适用)对于模型 化合物的解释将借助构象 用经验势函数进行能量计算。核磁共振 耦合常数和n.o.E.将从 低能分子构象的坐标 与实验数据进行了比较。内部运动的证据 并将寻求低聚糖的分子灵活性与 1-6连杆机构随温度变化的实验研究 并用核磁共振弛豫法测定了它们的构象。 不含NO的柔性分子的构象计算 单低能构象将使用统计蒙特卡罗 方法：研究方法。对非粘合、静电和非粘合的贡献 疏水相互作用对分子作用力的影响 观测到的构象将通过实验确定 在非水溶剂中的构象测量 计算方法。