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首页> 外文期刊>Journal of Medicinal Chemistry >Conformations and Receptor Activity of Desmopressin Analogues, Which Contain gamma-Turn Mimetics or a Psi(CH(2)O) Isostere.
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Conformations and Receptor Activity of Desmopressin Analogues, Which Contain gamma-Turn Mimetics or a Psi(CH(2)O) Isostere.

机译：去氨加压素类似物的构型和受体活性，其中包含γ-转模拟物或Psi（CH（2）O）等排物。

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摘要

Three analogues of the antidiuretic drug desmopressin ([1-desamino,8-D-arginine]vasopressin) have been prepared. In two of these, gamma-turn mimetics based on a morpholin-3-one framework have been inserted instead of residues Phe3-Asn5, whereas the third analogue has a methylene ether isostere in place of the amide bond between residues 3 and 4. The three analogues were used to probe if the structure determined for desmopressin in aqueous solution, which contains an inverse gamma-turn centered around Gln4, is important in interactions with the vasopressin V(2) receptor. Conformational studies revealed that the analogues that contain either an inverse gamma-turn mimetic or a methylene ether isostere mimicked the conformation of desmopressin fairly well and very well, respectively. Despite this, the analogues displayed only very low agonistic activities at the vasopressin V(2) receptor. Consequently, an inverse gamma-turn involving residues Phe3-Asn5 does not appear to be important when desmopressin is bound to the V(2) receptor. In addition, it was concluded that the amide bond between Phe3 and Gln4 in desmopressin is crucial for interactions with the antidiuretic V(2) receptor.
机译：已经制备了抗利尿药去氨加压素的三种类似物（[1-去氨基，8-D-精氨酸]加压素）。在其中的两个中，已插入基于吗啉-3-酮骨架的γ-转类似物，而不是残基Phe3-Asn5，而第三个类似物在残基3和4之间具有亚甲基醚等排物取代酰胺键。三个类似物被用来探测确定去氨加压素在水溶液中的结构是否包含以Gln4为中心的反伽马转角，在与加压素V（2）受体的相互作用中是否重要。构象研究表明，含有反向伽马转模拟物或亚甲基醚等排体的类似物分别很好地模拟了去氨加压素的构象。尽管如此，类似物在加压素V（2）受体上只显示出非常低的激动活性。因此，当去氨加压素与V（2）受体结合时，涉及残基Phe3-Asn5的反向伽马转似乎并不重要。此外，得出的结论是，去氨加压素中Phe3和Gln4之间的酰胺键对于与抗利尿剂V（2）受体的相互作用至关重要。

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