PROTEIN INHIBITORS OF CALCIUM PHOSPHATE PRECIPITATION

人类唾液中的钙是过饱和的 形成牙釉质的磷酸盐，这种情况会 通常会产生不需要的和可能有害的降水 唾液腺和牙齿上的磷酸钙盐类。 这些不良副作用可以通过唾液预防。 磷蛋白、他汀蛋白和酸性富含脯氨酸的蛋白 (PRP)，这是磷酸钙的有效抑制剂 降水。由于它们的活动，唾液提供了一种 预期的、可修复的但稳定的环境，这很重要 以保持牙齿的健康。我们的目标是 充分了解这些保护性和修复性 功能，将它们与口腔健康和疾病联系起来，并 达到一定的知识水平，这将有助于确保 自然的口腔防御机制在 嘴。申请者和联合调查员之前的研究 关于他汀类和PRP类药物的鉴定 磷酸钙的沉淀，对 确定了它们的结构，并取得了实质性进展 朝着建立分子机制的方向发展，通过这些机制 不寻常的大分子行为。现在有人提议将 对这些功能和作用机制的理解 以下列方式合成分子：1)通过合成磷丝氨酸- 含有斯塔瑟林的多肽类似物和结构的PRP 研究b)通过研究后翻译的机制 丝氨酸对史泰林和PRP的磷酸化作用 含有专门为此而合成的多肽类似物 目的，3)通过研究斯坦瑟林和PRP的类似物 非人类哺乳动物将进一步了解结构功能 这些分子的关系和进化方面，以及4) 通过研究史坦丁的行为和命运的特定方面 PRP在口腔中，这是他们的重要位置 行动，但在他们容易被口腔微生物群降解的地方。 这项工作将利用现代气相加以推进。 微测序方法与固相多肽合成 技巧。这项工作将带来对 一种重要的牙齿保护系统和对牙齿的新认识 专一性和特异性对磷酸钙化学的调控 不寻常的磷蛋白。

Human saliva is supersaturated with respect to the calcium phosphate salts which form dental enamel, a condition which would normally generate unwanted and potentially harmful precipitation of calcium phosphate salts in the salivary glands and on the teeth. These, undesirable side effects are prevented by 2 salivary phosphoprotein, statherin and the acidic proline-rich proteins (PRP), which are potent inhibitors of calcium phosphate precipitation. Because of their activities, saliva provides a prospective, reparative but stable environment which is important for maintaining the health of the teeth. Our objectives are to gain a sound understanding of these protective and reparative functions, to relate them to oral health and disease, and to achieve a level of knowledge which will help to ensure that these natural oral defense mechanisms fully express themselves in the mouth. Previous studies by the applicant and co-investigators led to the identification of statherin and the PRP's as inhibitors of calcium phosphate precipitation, made a major contribution to the determination of their structures, and made substantial advances towards establishing the molecular mechanisms by which these unusual macromolecule act. It is now proposed to advance understanding of these functions and mechanisms of action of these molecules in the following ways: 1) by synthesizing phosphoserine- containing peptide analogs of statherin and the PRP's for structure studies b) by investigating mechanisms of post-translational phosphorylation of statherin and the PRP's by using serine- containing peptide analogs specifically synthesized for this purpose, 3) by studying analogs of statherin and the PRP's from nonhuman mammals to gain further insights into structure-function relationships and evolutionary aspects of these molecules, and 4) by studying specific aspects of the behavior and fate of statherin and the PRP's in the oral cavity, an important site at which they act but where they are subject to degradation by oral microflora. The work will be advanced by use of modern gas-phase microsequencing methods and solid phase peptide synthesis techniques. From this work will come advances in understanding of an important tooth-protective system and new knowledge of the modulation of the chemistry of calcium phosphates by specific and unusual phosphoprotein.