Conformationally constrained cyclic enkephalin analogs with pronounced delta opioid receptor agonist selectivity.
Conformationally constrained cyclic enkephalin analogs with pronounced delta opioid receptor agonist selectivity.
复制标题
构象受限的环状脑啡肽类似物，具有显着的 δ 阿片受体激动剂选择性。
DOI：
10.1016/0024-3205(83)90239-4
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发表时间：
1983
期刊：
影响因子：
6.1
通讯作者：
Yamamura,HI
中科院分区：
文献类型：
--
作者：
Mosberg,HI;Hurst,R;Hruby,VJ;Galligan,JJ;Burks,TF;Gee,K;Yamamura,HI
脑啡肽类似物[D-Pen 2，L-Cys 5]-和[D-Pen 2，D-Cys 5]-脑啡肽是环状化合物，受其14元二硫环和青霉胺侧链β，β二甲基取代基刚性作用的限制。这些类似物在豚鼠回肠和小鼠输精管系统中的相对效价分别是后者的666倍和215倍，显示出深刻的δ受体特异性。相反，在无钠的大鼠脑结合试验中测得的受体选择性要温和得多，环状类似物取代[~3H][D-Ala_2，D-Leu_5]脑啡肽的效率分别是[~3H]纳洛酮的15.2倍和6.0倍。然而，对于在与GPI和MVD分析相同的钠浓度下进行的结合分析，这些结合选择性分别增加到167和49。
The enkephalin analogs,[D-Pen 2, L-Cys 5]-and [D-Pen 2, D-Cys 5]-enkephalin are cyclic compounds, conformationally constrained by virtue of their 14-membered, disulfide containing rings and by the rigidizing effect of the β, β dimethyl substituents of the penicilamine side chain. The analogs exhibit profound δ receptor specificity as assessed by their relative potencies in the guinea pig ileum (GPI) and mouse vas deferens (MVD) assays, exhibiting, respectively, 666 and 215 times higher potency in the latter assat system. By contrast, the receptor selectivities measured in rat brain binding assays in the absence of sodium were much more modest, the cyclic analogs being, respectively, 15.2 and 6.0 times more effective at displacing [3 H][D-Ala 2, D-Leu 5] enkephalin than [3 H] naloxone. However, for binding assays performed in the presence of a sodium concentration equivalent to that used in the GPI and MVD assays, these binding selectivities increased to 167 and 49, respectively.