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首页> 外文期刊>Journal of Molecular Biology >Preferred conformation of endomorphin-1 in aqueous and membrane-mimetic environments.
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Preferred conformation of endomorphin-1 in aqueous and membrane-mimetic environments.

机译：在水和膜模拟环境中，endomorphin-1的优选构型。

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摘要

The newly discovered endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) are potent opioid peptides with the highest affinity and selectivity for the mu receptor among all known endogenous ligands. To investigate a possible correlation between these biological properties and the conformational preferences of the small peptides, a comparative structural analysis was performed of endomorphin-1 in aqueous buffer and in membrane-mimicking SDS and AOT normal and reverse micelles by the use of CD, FT-IR, fluorescence and(1)H-NMR spectroscopy. It is well established for opioid peptides that, independently of the receptor selectivity, the Tyr1 residue plays the role of the primary pharmacophore and that the orientation of the second aromatic pharmacophore relative to the tyrosine side-chain dictates the mu or delta-receptor selectivity. By varying the environment of endomorphin-1 from water to the amphipathic SDS micelles and even more efficiently to the AOT reverse micelles, the display of the aromatic side-chains changes from an interaction of the Tyr1 and Phe4 residues to a switch of the Trp3 indole group into close contact with the phenolic moiety to prevent this type of interaction and to force an orientation of the Phe4 side-chain into the opposite direction. This conformational switch is accompanied by a stabilization of the cis -Pro2 isomer and the resulting spatial array of the pharmacophoric groups correlate well with the structural model of mu receptor-bound opioid peptides. The results indicate that AOT reverse micelles with a woof 10, where almost exclusively ordered water is secluded in the cavity, constitute with their electrostatic and hydrophobic potential an excellent mimetic of amphipathic surfaces as present on lipid bilayers and on ligand-recognition and ligand-binding sites of proteins. Copyright 1999 Academic Press.
机译：新发现的endomorphin-1（Tyr-Pro-Trp-Phe-NH2）和endomorphin-2（Tyr-Pro-Phe-Phe-NH2）是有效的阿片类肽，对mu受体的亲和力和选择性在所有已知内源性中最高配体。为了研究这些生物学特性与小肽的构象偏好之间的可能相关性，使用CD，FT对水性缓冲液和模拟SDS和AOT正常和反胶束的膜中的内啡肽-1进行了比较结构分析-IR，荧光和（1）H-NMR光谱。对于阿片样物质肽已经很好地确定，与受体选择性无关，Tyr1残基起主要药效基团的作用，并且第二芳香族药效基团相对于酪氨酸侧链的方向决定了mu或delta受体的选择性。通过从水到两亲SDS胶束，甚至更有效地改变AOT反向胶束的内啡肽1的环境，芳香族侧链的展示方式从Tyr1和Phe4残基的相互作用变为Trp3吲哚的转换。基团与酚部分紧密接触以防止这种相互作用并迫使Phe4侧链的取向朝相反的方向。该构象转换伴随有顺式-Pro2异构体的稳定化，并且药效基团的所得空间排列与μ受体结合的阿片样肽的结构模型很好地相关。结果表明，带有woof 10的AOT反胶束几乎排在空腔中，几乎是唯一有序的水，它们的静电和疏水势能构成脂质双层，配体识别和配体结合上存在的两亲性表面的极佳模拟物蛋白质的位点。版权所有1999，学术出版社。

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