Selection of progesterone derivatives specific to membrane progesterone receptors
Selection of progesterone derivatives specific to membrane progesterone receptors
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膜孕酮受体特异性孕酮衍生物的选择
DOI：
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发表时间：
2017
期刊：
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通讯作者：
O. Smirnova
中科院分区：
文献类型：
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作者：
A. V. Polikarpova;A. Maslakova;I. Levina;L. E. Kulikova;Yu. V. Kuznetsov;A. Guseva;T. A. Shchelkunova;I. Zavarzin;O. Smirnova
膜孕酮受体（mPRs）的选择性激动剂和拮抗剂的搜索是由mPRs介导的孕酮信号转导机制的研究的起点，不同于核受体。根据初步数据，mPRs的配体亲和力显着不同于经典的核孕酮受体（nPRs），这可能表明这些蛋白质的配体结合口袋的结构差异。在目前的工作中，我们分析了几种孕酮衍生物的亲和力的人胰腺癌BxPC 3细胞系，其特征在于高水平的mPR mRNA的表达和nPR mRNA的表达的情况下的mPR。将这些值与这些化合物对nPR的亲和力进行比较。所有测试的化合物显示几乎没有亲和力的nPR，而它们对mPR的选择性是不同的。具有额外的19-羟基和去除的3-酮基的衍生物对mPR具有最高的选择性。这些结果表明，这些化合物作为最具选择性的孕酮类似物，用于研究通过mPR的孕酮作用的机制。
The search of selective agonists and antagonists of membrane progesterone receptors (mPRs) is a starting point for the study of progesterone signal transduction mechanisms mediated by mPRs, distinct from nuclear receptors. According to preliminary data, the ligand affinity for mPRs differs significantly from that for classical nuclear progesterone receptors (nPRs), which might indicate structural differences in the ligand-binding pocket of these proteins. In the present work, we analyzed the affinity of several progesterone derivatives for mPRs of human pancreatic adenocarcinoma BxPC3 cell line that is characterized by a high level of mPR mRNA expression and by the absence of expression of nPR mRNA. The values were compared with the affinity of these compounds for nPRs. All tested compounds showed almost no affinity for nPRs, whereas their selectivity towards mPRs was different. Derivatives with an additional 19-hydroxyl group and removed 3-keto group had the highest selectivity for mPRs. These results suggest these compounds as the most selective progesterone analogs for studying the mechanisms of progestin action via mPRs.