500-MHZ PROTON NMR-STUDIES OF THE MEDIUM-DEPENDENT CONFORMATIONAL PREFERENCE OF PROSTAGLANDIN-F 2-ALPHA ANALOGS
500-MHZ PROTON NMR-STUDIES OF THE MEDIUM-DEPENDENT CONFORMATIONAL PREFERENCE OF PROSTAGLANDIN-F 2-ALPHA ANALOGS
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DOI：
10.1021/bi00330a032
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发表时间：
1985-01-01
期刊：
影响因子：
2.9
通讯作者：
LIN, BS
中科院分区：
文献类型：
--
作者：
ANDERSEN, NH;LIN, BS
前列腺素 F2.alpha 2-10 mM D2O 溶液的 1H NMR 谱的完整分配。介绍了 (PGF2.alpha.)、其 C-15 差向异构体以及在 C-16 或 C-17 处带有偕二甲基基团的类似物。 PGF2.α。在CDCl3溶液中对其1,9-和1,15-内酯进行了类似的研究。这些作业是根据广泛的标量解耦和差异 NOE（核欧沃豪塞效应）光谱以及对特定氘代类似物的检查得出的。这些研究还定义了每个系统中从 C-5 到 C-16 的构象（包括环戊烷假旋转偏好）。大环内酯类在C-4.fwdarw处表现出很少或没有构象自由度。 C-1，但广泛的旋转平均发生在单环化合物中两个侧链的末端部分。如此确定的构象特征与晶体结构中所见的构象特征以及假定在结合PGF2α-识别受体时发生的构象特征形成对比。 NMR数据与DeTitta假设相反，即C-13、14π-键节点平面相对于环戊烷环和C-15.sbd.O键的方向的变化是PGF2.α-特异性受体的识别决定因素，并且解释了先前报道的介质依赖性手性光谱变化。
The complete assignments of the 1H NMR spectra of 2-10 mM D2O solutions of prostaglandin F2.alpha. (PGF2.alpha.), its C-15 epimer, and analogs bearing a gem-dimethyl group at C-16 or C-17 are presented. PGF2.alpha. and its 1,9- and 1,15-lactones were similarly studied in CDCl3 solution. The assignments follow from extensive scalar decoupling and difference NOE [nuclear Overhauser effect] spectra and the examination of a specifically deuterated analog. These studies also define the conformation (including cyclopentane pseudorotational preference) from C-5 through C-16 in each system. The macrolides show little or no conformational freedom at C-4 .fwdarw. C-1, but extensive rotational averaging occurs in the terminal portions of both side chains in the monocyclic compounds. The conformational features so determined are contrasted to those seen in crystal structures and those postulated to occur upon binding to PGF2.alpha.-recognizing receptors. The NMR data run counter to the DeTitta hypothesis that changes in the orientation of the C-13, 14 .pi.-bond nodal plane relative to the cyclopentane ring and the C-15.sbd.O bond are recognition determinants at PGF2.alpha.-specific receptors and account for the medium-dependent chiroptical spectral changes previously reported.