PROTEIN CHEMICAL STUDIES OF THE FORMS OF HCG

HCG 形式的蛋白质化学研究

• 批准号: 6108364
• 负责人: Steven Birken
• 金额: $ 22.64万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6108364
• 关键词: Macaca mulatta; chorionic gonadotropin; conformation; crystallization; disease /disorder model; disulfide bond; female; glycoprotein structure; gonadotropins; hormone receptor; human pregnant subject; laboratory mouse; luteinizing hormone; monoclonal antibody; ovulation; peptide hormone metabolism; postmenopause; pregnancy loss; protein folding; protein metabolism; protein purification; proteolysis; receptor binding; toxicology

The goals of this project are to apply protein chemistry to enhance our understanding of the nature of the crystallized form of hCG, to produce a properly folded hCG receptor fragment for three dimensional studies, and to determine the structures in serum and urine of hCG metabolites useful for diagnosis of diseases of reproduction. Hormone metabolic products have been shown to vary in pathological states and we intend to define the structures of such metabolites to improve their measurement and the understanding of their relationship to normal and abnormal physiology. This project combines our chemical capabilities to purify and structurally analyze minute quantities of proteins with our ability to develop and apply assays for measurement of these proteins. One major theme of this program is the collaborative studies with Projects II and III in an effort to produce properly-folded extracellular CG receptors for studies of the structure of the hormone-receptor interface. A second major theme is to determine the structures of hCG and hLH metabolites as markers of normal pregnancy, diseases of pregnancy and menopause. A third is to develop a nonhuman primate model of early pregnancy loss, EPL (loss of a chemically-detected pregnancy without any clinical evidence of pregnancy). The latter problem, resulting in a decline in human fertility, is a major social concern since it can result from exposure to environmental toxins. Our specific aims are to: (1) Perform Protein Chemical Studies Related to the Three-Dimensional Structures of the Gonadotropins and Their Receptors; (2) Isolate and determine the structures of forms of hCG and hLH from normal pregnant women, women with ectopic pregnancies, women undergoing ovulation induction and postmenopausal women; and (3) Develop and employ a primate model for the study of reproductive toxicology.

该项目的目标是应用蛋白质化学来增强我们的 了解人绒毛膜促性腺激素结晶形式的性质，以生产 用于三维研究的适当折叠的hCG受体片段， 并测定血清和尿液中hCG代谢物的结构。 对生殖疾病的诊断很有用。激素代谢 产品已被证明处于不同的病理状态，我们打算 定义此类代谢物的结构以改进其测量 以及对它们与正常和异常的关系的理解 生理学。这个项目结合了我们的化学能力来净化 用我们的能力对微量的蛋白质进行结构分析 开发和应用测定这些蛋白质的分析方法。 这个项目的一个主要主题是与 项目II和III，以努力生产适当折叠的细胞外 CG受体用于激素受体结构的研究 界面。第二个主要主题是确定hCG和hCG的结构 促黄体生成素代谢物作为正常妊娠、妊娠疾病和 更年期。第三个是发展早期的非人类灵长类动物模型。 妊娠丢失，EPL(化学检测到的妊娠丢失，没有 怀孕的临床证据)。后一个问题，导致 人类生育率的下降是一个主要的社会问题，因为它可能导致 暴露在环境毒素中。我们的具体目标是：(1) 进行与三维结构相关的蛋白质化学研究 促性腺激素及其受体的结构；(2)分离和 正常妊娠人绒毛膜促性腺激素和促黄体生成素形态结构的测定 妇女、宫外孕妇女、排卵妇女 引产和绝经后妇女；以及(3)发展和使用灵长类动物 生殖毒理学研究的模型。