CONFORMATION OF DENTALLY RELEVANT SALIVARY MOLECULES

这个项目的长期目标是定义 唾液分子的构象和它们的 生物功能。初步研究将集中在两个分子上 在腮腺唾液中发现：(A)富含酪氨酸的磷蛋白， 和(B)富含脯氨酸的糖蛋白“PRG”。这个 对这项研究最重要的生物学功能 关于他汀类药物的是对磷酸钙的调节 唾液和牙齿表面之间的平衡。关于 PRG，与这个项目相关的生物学功能是 口腔和咀嚼中的细菌清除 润滑剂。基于经验的方法将用于 结构分析是核磁共振(核磁共振)， 圆二色谱(CD)、紫外/可见光(UV/VIS)和 荧光光谱仪。以理论为基础的程序 对于构象的说明将包括对 通过能量最小化产生的量化结果和 由计算机生成的分子结构的目视检查 模特儿。将这些特殊方法应用于 前述唾液分子已经提供了 关于N-的构象的详细信息 并有望进一步阐明PRG的糖基化位点。 天然他汀类药物的三维结构 PRG中的功能域。简而言之，这些的程序 结构分析涉及首先检查光学(例如，金属 离子、盐、pH、温度、杂色剂、化学探针、 其他大分子等)。此信息提供了以下数据 的主体二级和三级结构 蛋白质/多肽。然后用核磁共振光谱学来阐明 原子水平上的构象和进一步的改进 由计算机模拟程序派生而来。已选择 然后对天然分子的片段进行生物测试。 活跃性和结构性分析。在这种方式下，最低限度 功能结构域仍然保留了生物活性 母体分子可以分离出来。一旦这件事完成， 制备和测试类似物以增强生物活性 在体外测试系统中。一个这样的拟议功能 目前正在研究的结构域是环状新糖肽 类似于PRG的N-糖基化位点。最终，这些 类似物将被用来帮助清除致病原 患者口腔和合成唾液中的细菌 有唾液功能障碍。

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.