BIS-PENICILLAMINE ENKEPHALINS POSSESS HIGHLY IMPROVED SPECIFICITY TOWARD DELTA-OPIOID RECEPTORS
BIS-PENICILLAMINE ENKEPHALINS POSSESS HIGHLY IMPROVED SPECIFICITY TOWARD DELTA-OPIOID RECEPTORS
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DOI：
10.1073/pnas.80.19.5871
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发表时间：
1983-01-01
期刊：
影响因子：
--
通讯作者：
BURKS, TF
中科院分区：
文献类型：
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作者：
MOSBERG, HI;HURST, R;BURKS, TF
构象受限、环状、含二硫的脑啡肽类似物[2- d -青霉胺-5- l -青霉胺]-脑啡肽。和[2- d -青霉胺-5- d -青霉胺]-脑啡肽。采用固相法合成。这些类似物对一类阿片受体的选择性通过检测小鼠输精管实验的相对效力来研究，其中功能受体为。delta。受体，与豚鼠回肠试验相比，在回肠试验中。受体是功能性受体，并通过确定它们的相对能力来取代原型。受体配体[D-Ala2-D-Leu5]-脑啡肽和原型。大鼠脑膜制剂中的受体配体纳洛酮。**图**。和* *图形* *。.delta展出。在生物实验中，受体选择性分别为1088和3164，在结合实验中，受体选择性分别为371和175。与之前报道的。delta。受体选择性类似物，[D-Ala2-D-Leu5]-脑啡肽，[D-Ser2-Leu5-Thr6]-脑啡肽和[D-Thr2-Leu5-Thr6]-脑啡肽，含有双笔的类似物提供了一个数量级的增加。受体选择性。
The conformationally restricted, cyclic, disulfide-containing, enkephalin analogs [2-D-penicillamine-5-L-penicillamine]-enkephalin .**GRAPHIC**. and [2-D-penicillamine-5-D-penicillamine]-enkephalin .**GRAPHIC**. were synthesized by solid-phase methods. Selectivities of these analogs for a single class of opioid receptor were investigated by examining relative potencies in the mouse vas deferens assay, in which the functional receptor is the .delta. receptor, vs. the guinea pig ileum assay, in which the .mu. receptor is the functional receptor and by determining their relative abilities to displace the prototypical .delta. receptor ligand [D-Ala2-D-Leu5]-enkephalin and the prototypical .mu. receptor ligand naloxone from rat brain membrane preparations. .**GRAPHIC**. and .**GRAPHIC**. exhibited .delta. receptor selectivities of 1088 and 3164, respectively, in the bioassays, and 371 and 175, respectively, in the binding assays. Compared with the previously reported .delta. receptor selective analogs, [D-Ala2-D-Leu5]-enkephalin, [D-Ser2-Leu5-Thr6]-enkephalin and [D-Thr2-Leu5-Thr6]-enkephalin, the bis-Pen-containing analogs provide an order of magnitude increase in .delta. receptor selectivity.