Rego Jean Luc Do, Leprince Jérôme, Luu-The Van, Pelletier Georges, Tonon Marie-Christine, Vaudry Hubert
INSERM U413, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research (IFRMP 23), University of Rouen, 76821 Mont-Saint-Aignan, France.
J Med Chem. 2007 Jun 28;50(13):3070-6. doi: 10.1021/jm0610548. Epub 2007 Jun 6.
We have previously shown that the endozepine octadecaneuropeptide (ODN) stimulates the biosynthesis of neurosteroids from frog hypothalamic explants. In the present study, we have investigated the structure-activity relationships of a series of analogs of the C-terminal octapeptide of ODN (OP) on neurosteroid formation. We found that OP and its cyclic analog cyclo1-8OP stimulate in a concentration-dependent manner the synthesis of various steroids including 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone and dehydroepiandrosterone. Deletion or Ala-substitution of the Arg1 or Pro2 residues of OP did not affect the activity of the peptide. In contrast, deletion or replacement of any of the amino acids of the C-terminal hexapeptide fragment totally abolished the effect of OP on neurosteroid biosynthesis. The present study indicates that the C-terminal hexapeptide of ODN/OP is the minimal sequence retaining full biological activity on steroid-producing neurons.
我们之前已经表明，内源性阿片样物质十八烷神经肽（ODN）可刺激青蛙下丘脑外植体中神经甾体的生物合成。在本研究中，我们研究了一系列ODN C末端八肽（OP）类似物对神经甾体形成的构效关系。我们发现，OP及其环状类似物环1-8OP以浓度依赖的方式刺激包括17-羟孕烯醇酮、孕酮、17-羟孕酮和脱氢表雄酮在内的各种甾体的合成。OP的Arg1或Pro2残基缺失或被丙氨酸取代不会影响该肽的活性。相反，C末端六肽片段中任何氨基酸的缺失或替换都会完全消除OP对神经甾体生物合成的影响。本研究表明，ODN/OP的C末端六肽是在甾体生成神经元上保留完整生物活性的最小序列。
