STRUCTURE AND FUNCTION OF PREGNANCY RECOGNITION HORMONE

绵羊对怀孕的母体识别依赖于分泌 绵羊滋养层蛋白-1(OTP-1)。在第13天至 怀孕21天，OTP-1是主要的妊娠分泌产物， 它与子宫前列腺素F2pha的抑制有关 分泌物。OTP-1抑制血管紧张素转换酶的搏动性分泌 子宫内的前列腺素F2a可以维持子宫的体部 黄体持续分泌黄体酮。猪和牛 研究表明，妊娠也会产生类似的抗黄体溶解作用。 代理人，以及人类的等价物也被假设为。OTP-1具有 最近被证明与α干扰素有相同的氨基酸同源性。 因此，OTP-1参与了胚胎和胚胎之间的相互作用 母体系统，导致适当的内分泌和 妊娠早期的免疫反应。 我们建议检查妊娠的结构/功能基础。 利用合成的OTP-1识别和其他生物学效应 用于直接受体竞争和生产的多肽方法 抗OTP-1和OTP-1合成肽的单抗。它是 计划通过以下办法实现这一目标： (1)进行竞争性受体结合和功能实验 在合成肽和OTP-1之间进行比较，并确定其对 与OTP-1受体结合的合适的多肽；特别强调 将使用较长的多肽(可能的区域)；(2) 通过系统修饰受体竞争中重要的多肽 去除和/或取代氨基酸，以便更准确地 确定与功能相关的OTP-1序列或区域： (3)制备抗OTP-1的单抗并检测其能力 阻断OTP-1的功能和/或与膜受体的结合；(4)MAP 用人工合成的方法检测这些单抗的表位特异性 对应于位于OTP-1分子上的区域的肽 表面；(5)利用合成肽产生位点特异性的单抗 和多克隆抗体，并确定它们对功能和 OTP-1与受体的结合：(6)确定OTP-1的空间关系 通过竞争结合，OTP-1的表位(以及不同的区域) 确定表位的单抗(及其Fab片段)之间的相互作用 OTP-1的特性。拟议的研究很重要，因为它们 将提供有关怀孕的结构基础的信息 OTP-1的识别和抗病毒特性。

Maternal recognition of pregnancy in sheep is dependent upon secretion of ovine trophoblast protein-1 (oTP-1) by the conceptus. Between days 13 and 21 of pregnancy, oTP-1 represents the major conceptus secretory product, and it is responsible for inhibition of uterine prostaglandin F2alpha secretion. The oTP-1-induced inhibition of pulsatile secretion of prostaglandin F2alpha by the uterus allows for maintenance of the corpus luteum with continued secretion of progesterone. Porcine and bovine conceptuses have also been shown to produce similar antiluteolytic agents, and a human equivalent has been postulated as well. oTP-1 has recently been shown to share amino acid homology with alpha interferons. Thus, oTP-1 is involved in the interaction between the conceptus and maternal systems which results in appropriate endocrinological and immunological responses in early pregnancy. We propose to examine the structure/function basis for pregnancy recognition and other biological effects of oTP-1 using the synthetic peptide approach for both direct receptor competition and production of monoclonal antibodies to oTP-1 and oTP-1 synthetic peptides. It is planned that the objective be achieved through the following approach: (1) perform competitive receptor binding and functional experiments between synthetic peptides and oTP-1, and determine the ability of appropriate peptides to bind to the oTP-1 receptors; particular emphasis will be placed on the use of longer peptides (possible domains); (2) modify peptides that are important in receptor competition by systematic removal and/or substitution of amino acids in order to more precisely identify sequences or regions of oTP-1 that are involved in functions: (3) generate monoclonal antibodies to oTP-1 and determine their ability to block function and/or binding of oTP-1 to membrane receptors; (4) map the epitope specificity of these monoclonal antibodies using synthetic peptides that correspond to regions of the oTP-1 molecule located on the surface; (5) use synthetic peptides to produce site specific monoclonal and polyclonal antibodies and determine their effect on functions and receptor binding by oTP-1: (6) determine the steric relationship of epitopes, (and thus various regions) of oTP-1 by competitive binding between monclonal antibodies (and their Fab fragments) of defined epitope specificities with oTP-1. The proposed studies are important because they will provide information on the structural basis for pregnancy recognition and the antiviral properties of oTP-1.