CONFORMATION OF DENTALLY RELEVANT SALIVARY MOLECULES

牙齿相关唾液分子的构象

• 批准号: 3072162
• 负责人: RONALD E LOOMIS
• 金额: $ 5.44万
• 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/3072162
• 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.

该项目的长期目标是定义关系 唾液分子的构象及其结构之间的关系 生物学功能。 初步研究将集中于两个分子 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 对本研究最重要的生物学功能 关于富酪蛋白是磷酸钙的调节 唾液和牙齿表面之间的平衡。 关于 PRG，与该项目的生物学相关功能是 口腔和咀嚼过程中的细菌清除 润滑。 所使用的基于经验的方法 结构分析是核磁共振（NMR）， 圆二色性 (CD)、紫外/可见光 (UV/VIS) 和 荧光光谱。 基于理论的程序 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 计算机生成的分子结构的目视检查 造型。 这些特定方法的应用 上述唾液分子已经提供了 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 天然富酪素和其他物质的三维结构 PRG 中的功能域。 简单来说一下这些的流程 结构分析首先涉及检查光学（例如金属 离子、盐、pH、温度、离液剂、化学探针、 其他大分子等）。 该信息提供了以下数据： 的大量二级和三级结构 蛋白质/肽。 然后使用 NMR 光谱来阐明 原子水平上的构象进一步细化 来自计算机建模程序。 已选择 然后对天然分子的片段进行生物学测试 活动并进行结构分析。 这样最小的 功能域仍保留其生物活性 可以分离母体分子。 一旦完成此操作， 制备并测试类似物以增强生物活性 在体外测定系统中。 一种这样的建议功能 目前正在研究的结构域是环状新糖肽 PRG 的 N-糖基化位点的类似物。 最终，这些 类似物将被用作清除病原体的辅助剂 来自口腔和患者合成唾液中的细菌 伴有唾液功能障碍。