THE STRUCTURAL BASIS OF RELAXIN ACTION

放松作用的结构基础

• 批准号: 3324232
• 负责人: christian none schwabe
• 金额: $ 12.37万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1991-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3324232
• 关键词: chemical structure function; drug design /synthesis /production; drug metabolism; genetic library; gestational diabetes mellitus; guinea pigs; hormone receptor; hormone regulation /control mechanism; insulin; laboratory mouse; laboratory rabbit; peptide hormone; relaxin; sperm motility

Relaxin is an ovarian peptide hormone that is responsible for those tissue modifications that result in birth canal widening just prior to parturition. Relaxin is produced in the corpus luteum of pregnancy or in the placenta and is a disulfide homolog of insulin that exhibits neither biological insulin activity nor crossreactivity to antibodies raised against insulin. Besides the involvement in parturition relaxin may play a role in fertility in that the implantation of an ovum into the endometrium appears to be a relaxin-mediated process and sperm motility appears to be enhanced in the presence of relaxin. It has also been reported that relaxin exhibits an insulin-sparing activity during pregnancy and thus may be a potential drug for the treatment of pregnancy diabetes. The studies proposed here are aimed at an understanding of the relationship of relaxin structure to its various functions. The plan is to chemically dissect and reconstitute various aspects of the relaxin surface and to measure the effect of such modifications on the structural integrity and the biological activity of the molecule. One of the immediate goals is to identify the receptor interaction site of relaxin and to modify this interaction site in such a way that a covalent link with the receptor may be established. Chemical recognition sites have been added to the relaxin molecule in places where they do not interfere with biological activity and these sites should now serve to isolate the covalently-linked relaxin receptor complex. Attempts will then be made to obtain partial sequence information concerning the relaxin receptor that would eventually aid in the construction of a nucleotide probe with which a relaxin receptor-coding sequence may be isolated from the appropriate gene library.

松弛素是一种卵巢肽激素， 那些导致产道变宽的组织改变 在分娩之前。 松弛素产生于卵巢的黄体， 是胰岛素的二硫化物同系物 既没有生物胰岛素活性，也没有交叉反应性 抗胰岛素抗体。 除了参与 分娩松弛素可能在生育中起作用， 卵子植入子宫内膜似乎是一种 松弛素介导的过程和精子活力似乎是 在松弛素的存在下增强。 另据报道 松弛素在怀孕期间表现出节约胰岛素的活性， 因此可能是治疗妊娠的潜在药物 糖尿病 这里提出的研究旨在了解 松弛素结构与其各种功能的关系。 该计划 是用化学方法分解和重组 松弛素表面，并测量这种修饰的效果 对结构完整性和生物活性的影响 分子。 当前的目标之一是确定受体 松弛素的相互作用位点，并修饰该相互作用位点 以这种方式，与受体的共价连接可以 确立了习 化学识别位点已被添加到 松弛素分子在不干扰 生物活动，这些网站现在应该用来隔离 共价连接的松弛素受体复合物。 尝试将 以获得关于所述序列的部分序列信息。 松弛素受体，最终将有助于建立一个 松弛素受体编码序列的核苷酸探针 可以从适当的基因文库中分离。