Design of agonists and antagonists for opioid receptors based on the structures of endomorphins

我们合成了含有脯氨酸模拟物的[2 '，6'-二甲基-L-酪氨酸1]内吗啡肽2（EM-2）类似物。其中，[Dmt 1，L-Pip 2]EM-2是有效的选择性μ受体激动剂，[Dmt 1，Aze 2]EM-2是μ/δ受体激动剂。[Dmt1[Aze 2]EM-2在DMSO和H2O中均以顺式构象为主，顺式/反式比例为2：1。顺式[Dmt 1，Aze 2]EM-2构象呈折叠形式。类似物的进一步构象分析正在进行中。

We synthesized the [2',6'-Dimethyl-L-tyrosine1]endomorphin 2 (EM-2) analogues containing proline mimics. Among them, [Dmt1, L-Pip2]EM-2 was potent and selective mu-agonist, while [Dmt1, Aze2]EM-2 was mu/delta-agoinist. [Dmt1, Aze2]EM-2 had a cis/trans equilibrium of ratio 2:1 and cis conformer was predominant in both DMSO or H2 O. The cis [Dmt1, Aze2]EM-2conformers took folded form. The further conformational analyses of the analogues are in progress.