PROTEIN INHIBITORS OF CALCIUM PHOSPHATE PRECIPITATION

磷酸钙沉淀的蛋白质抑制剂

• 批准号: 2129326
• 负责人: DAVID H SCHLESINGER
• 金额: $ 17.35万
• 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/2129326
• 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.

人类唾液中的碱性钙高度饱和。 磷酸盐。然而，从唾液和唾液中沉淀这些盐 磷酸钙在牙釉质上不会发生晶体生长 正常的生理状态。这种出乎意料的稳定性是由于 他汀类两种唾液磷蛋白的抑制活性 和酸性富含脯氨酸的磷酸蛋白(PRP)。在生理上 条件下，他汀类药物抑制自发沉淀和晶体生长 磷酸钙，而PRP则是晶体的有效抑制物 通过吸附在钙磷酸盐矿物表面而生长，如 牙釉质矿物。这些活动在以下方面具有生物学意义 它们的作用是提供一个过饱和的，但稳定的，保护性的 牙釉质的修复环境，这对牙釉质 牙齿的完整性。 这个项目的基本目标是将 这些抑制物对它们在口腔中的功能有影响。最严谨的 解决这个问题的方法是通过化学合成这些类似物 新的磷酸蛋白及其类似物的活性研究 抑制磷酸钙盐的一次和二次沉淀。 最近，我们开发了一种新颖而有效的策略来准备任何 所需的他汀类和PRPS的合成含磷丝氨酸类似物 此外，还计划推出各种各样的此类类似产品。最近，它一直在 结果表明，当PRPS和他汀类药物吸附在磷灰石矿物上时， 可以促进几种突出的口腔细菌的黏附。 因此，我们也在计划化学合成类似物 施他林的C-末端和PRPS研究这些胶粘剂 分子水平上的反应。 我们正在继续研究这些抑制剂的演变，并正在 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。

项目成果

Corticotrophin-releasing factor in extra-hypothalamic brain of the mouse: demonstration by immunoassay and immunoneutralization of bioassayable activity.

小鼠下丘脑外脑中的促肾上腺皮质激素释放因子：通过生物测定活性的免疫测定和免疫中和来证明。

• DOI: 10.1677/joe.0.1110143
• 发表时间: 1986
• 期刊: The Journal of endocrinology
• 作者: Nakane,T;Audhya,T;Hollander,CS;Schlesinger,DH;Kardos,P;Brown,C;Passarelli,J
• 通讯作者: Passarelli,J

Levels of corticotropin releasing factor-like immunoreactivity in mammalian hypothalamic and extrahypothalamic brain tissue as determined with a monoclonal antibody to the ovine material.

使用针对绵羊材料的单克隆抗体测定哺乳动物下丘脑和下丘脑外脑组织中促肾上腺皮质激素释放因子样免疫反应性的水平。

• DOI: 10.1210/endo-112-6-2206
• 发表时间: 1983
• 期刊: Endocrinology
• 影响因子: 4.8
• 作者: Hollander,CS;Audhya,T;Russo,M;Passarelli,J;Nakane,T;Schlesinger,D
• 通讯作者: Schlesinger,D

Multiple non-repeated epitopes on the circumsporozoite protein of Plasmodium knowlesi.

诺氏疟原虫环子孢子蛋白上的多个非重复表位。

• DOI: 10.1016/0166-6851(85)90056-8
• 发表时间: 1985
• 期刊: Molecular and biochemical parasitology
• 影响因子: 1.5
• 作者: Vergara,U;Gwadz,R;Schlesinger,D;Nussenzweig,V;Ferreira,A
• 通讯作者: Ferreira,A

Structure of an immunodominant epitope of the circumsporozoite surface protein of Plasmodium knowlesi.

诺氏疟原虫环子孢子表面蛋白免疫显性表位的结构。

• DOI: 10.1021/bi00318a043
• 发表时间: 1984
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Schlesinger,DH;Cochrane,AH;Gwadz,RW;Godson,GN;Melton,R;Nussenzweig,RS;Nussenzweig,V
• 通讯作者: Nussenzweig,V