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， 通常会产生不需要的和潜在有害的降水 唾液腺和牙齿上的磷酸钙盐。 这些不良的副作用是防止2唾液 磷蛋白，statherin和酸性脯氨酸丰富的蛋白质 (PRP)，这是磷酸钙的有效抑制剂 降水 由于它们的活动，唾液提供了一个 具有前瞻性、修复性但稳定的环境， 保持牙齿的健康。 我们的目标为 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， 达到一定的知识水平，这将有助于确保这些 自然的口头防御机制充分表达自己在 嘴里 申请人和合作研究者之前的研究 用于鉴定作为抑制剂的雄甾苷和PRP， 磷酸钙沉淀，作出了重大贡献， 确定其结构，并取得了重大进展 以建立分子机制， 不寻常的大分子行为。 现拟推进 了解这些功能和作用机制， 通过以下方式合成分子：1）通过合成磷酸丝氨酸- 含有statherin的肽类似物和用于结构的PRP 研究B）通过研究翻译后的机制， 通过使用丝氨酸-丝氨酸蛋白酶磷酸化黑果苷和PRP， 含有专门为此合成的肽类似物 目的，3）通过研究Statherin的类似物和来自 非人类哺乳动物获得进一步的了解结构功能 这些分子的关系和进化方面，以及4） 通过研究斯塔德林的行为和命运的特定方面， 而PRP在口腔中，这是一个重要的部位， 但它们会受到口腔微生物菌群的降解。 现代气相色谱技术的应用将进一步推进这一工作 微测序方法和固相肽合成 技术. 从这项工作中，我们将进一步了解 一个重要的牙齿保护系统和新的知识 通过特定的和 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.