PROTEIN INHIBITORS OF CALCIUM PHOSPHATE PRECIPITATION

磷酸钙沉淀的蛋白质抑制剂

• 批准号: 3219895
• 负责人: DAVID H SCHLESINGER
• 金额: $ 15.79万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-02-01 至 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3219895
• 关键词: binding proteins; calcification inhibitor; calcium phosphate; chemical structure function; conformation; fluorescence spectrometry; nuclear magnetic resonance spectroscopy; oral bacteria; oral health; peptide analog; phosphoproteins; precipitation; protein biosynthesis; proteins; saliva; stoichiometry; tooth enamel

Human saliva is highly supersaturated with respect to basic calcium phosphate salts. However, precipitation of these salts from saliva and crystal growth of calcium phosphates onto dental enamel do not occur under normal physiological conditions. This unexpected stability is due to the inhibitory activities of two kinds of salivary phosphoproteins, statherin and the acidic proline-rich phosphoproteins (PRP). At physiological conditions, staterin inhibits spontaneous precipitation and crystal growth of calcium phosphates, whereas the PRP act as potent inhibitors of crystal growth by adsorbing onto surfaces of calcium phosphate minerals, such as dental enamel mineral. These activities are of biological significance in that they act to provide a supersaturated, but stable, protective and reparative environment for the dental enamel, which is important for the integrity of the teeth. The basic objective of this project is to relate the primary structure of these inhibitors to their functions in the oral cavity. The most rigorous way of attacking this problem is via chemical synthesis of analogs of these novel phosphoproteins and to study their activities of these analogs in inhibiting primary and secondary precipitation of calcium phosphate salts. Recently, we developed a novel and efficient strategy for preparing any desired synthetic phosphoserine-containing analog of staterin and the PRPs and a wide variety of such analogs are planned. Recently, it has been shown that the PRPs and statherin, when adsorbed onto apatitic minerals, can act to promote adhesion of several prominent oral bacteria. Consequently, we are also planning the chemical synthesis of analogs of the C-terminus of statherin and the PRPs to investigate these adhesive reactions on a molecular level. We are continuing to study the evolution of these inhibitors and are presently determining their structures in the saliva of the red kangaroo and other mammalian species.

人的唾液中碱性钙是高度过饱和的 磷酸盐 然而，这些盐从唾液中沉淀出来， 磷酸钙在牙釉质上的晶体生长不会在 正常的生理条件。 这种出乎意料的稳定性是由于 两种唾液磷蛋白的抑制活性 和酸性富脯氨酸磷蛋白（PRP）。 在生理 条件下，他汀抑制自发沉淀和晶体生长 磷酸钙，而PRP作为晶体的有效抑制剂 通过吸附在磷酸钙矿物表面上生长，例如 牙釉质矿物质。这些活动具有生物学意义， 它们的作用是提供一种过饱和的，但稳定的，保护性的， 修复环境的牙釉质，这是重要的 牙齿的完整性。 本项目的基本目标是将 这些抑制剂在口腔中发挥作用。 最严格的 解决这个问题的一种方法是通过化学合成这些类似物， 新的磷蛋白，并研究它们的活性，这些类似物在 抑制磷酸钙盐的初级和次级沉淀。 最近，我们开发了一种新颖而有效的策略，用于制备任何 所需的合成的含磷酸丝氨酸的他汀类似物和PRP 并且计划了多种这样的类似物。 近日有 显示PRP和Statherin，当吸附到磷灰石矿物上时， 可以促进几种主要口腔细菌的粘附。 因此，我们还计划化学合成的类似物的 C-末端的statherin和PRP研究这些粘合剂 分子水平上的反应。 我们正在继续研究这些抑制剂的演变， 目前正在确定它们在红袋鼠唾液中的结构 和其他哺乳动物物种。