CONFORMATION OF DENTALLY RELEVANT SALIVARY MOLECULES

牙齿相关唾液分子的构象

• 批准号: 3072166
• 负责人: RONALD E LOOMIS
• 金额: $ 6.89万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-06-01 至 1993-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3072166
• 关键词: circular dichroism; computer simulation; conformation; fluorescence spectrometry; glycopeptides; glycoproteins; glycosylation; mastication; mathematical model; nuclear magnetic resonance spectroscopy; parotid gland; phosphoproteins; proline; saliva; tyrosine; ultraviolet spectrometry

The long range goal of this project is to define the relationships between the conformation of salivary molecules and their biological functions. Initial studies will focus on two molecules found in parotid saliva: (A) the tyrosine-rich phosphoprotein, "statherin" and (B) the proline-rich glycoprotein, "PRG". The biological function of greatest importance to this study concerning statherin is the regulation of the calcium-phosphate equilibrium between saliva and the tooth's surface. Regarding PRG, the biologically relevant functions to this project are bacterial clearance from the oral cavity and masticatory lubrication. The empirically-based methods to be used for structural analyses are nuclear magnetic resonance (NMR), circular dichroism (CD), ultraviolet/visible (UV/VIS) and fluorescence spectroscopies. The theoretically-based procedures for elucidation of conformation will include both evaluation of the quantitative results produced through energy minimization and visual inspection of molecular structures generated by computer modeling. The application of these particular methodologies to the aforementioned salivary molecules has already provided detailed information concerning the conformation of the N- glycosylation sites of PRG and promises to further elucidate the three-dimensional structures of native statherin and other functional domains in PRG. Briefly, the procedure for these structural analyses involves first examining the optical (e.g. metal ions, salt, pH, temperature, chaotropic agents, chemical probes, other macromolecules, etc). This information provides data on the bulk secondary and tertiary structures of the proteins/peptides. NMR spectroscopy is then used to elucidate the conformation at the atomic level with further refinements derived from the computer modeling programs. Selected fragments of the native molecules are then tested for biological activity and structurally analyzed. In this way the minimum functional domain still retaining the biological activities of the parent molecule can be isolated. Once this is accomplished, analogs are prepared and tested for enhanced biological activities in the in vitro assay systems. One such proposed functional domain currently being investigated is a cyclic neoglycopeptide analog of the N-glycosylation sites of PRG. Ultimately, these analogs will be used as an aid for the clearance of pathogenic bacteria from the oral cavity and in synthetic salivas for patients with salivary dysfunction.

该项目的远距离目标是定义关系 在唾液分子的构象及其之间 生物功能。 最初的研究将集中于两个分子 在腮腺唾液中发现：（a）富含酪氨酸的磷蛋白， “ Statherin”和（B）富含脯氨酸的糖蛋白，“ PRG”。 这 这项研究最重要的生物学功能 关于Statherin是磷酸钙的调节 唾液和牙齿表面之间的平衡。 关于 PRG，该项目与生物学相关的功能是 口腔和咀嚼性的细菌清除率 润滑。 基于经验的方法用于 结构分析是核磁共振（NMR）， 圆二色性（CD），紫外线/可见（UV/VIS）和 荧光光谱。 理论上的程序 为了阐明构象，将包括对 通过能量最小化产生的定量结果和 视觉检查计算机生成的分子结构 造型。 这些特定方法的应用 上述唾液分子已经提供 有关n-构象的详细信息 PRG的糖基化位点，并有望进一步阐明 本地Statherin和其他的三维结构 PRG中的功能域。 简而言之 结构分析涉及首先检查光学（例如金属 离子，盐，pH，温度，交际剂，化学探针， 其他大分子等）。 此信息提供了有关的数据 批量的次级和第三结构 蛋白质/肽。 然后使用NMR光谱阐明 在原子水平上的构象和进一步的细化 源自计算机建模程序。 选定 然后对天然分子的片段进行生物学测试 活动和结构分析。 这样的最低限度 功能领域仍保留 可以隔离父分子。 一旦完成， 制备类似物并测试以增强生物学活动 在体外测定系统中。 一个这样提出的功能 当前正在研究的域是环状新糖肽 PRG的N-糖基化位点的类似物。 最终，这些 类似物将用作通知的帮助 口腔和患者合成唾液中的细菌 唾液功能障碍。