Novel analogues of enkephalin: indentification of functional groups required for biological activity.
Novel analogues of enkephalin: indentification of functional groups required for biological activity.
复制标题
脑啡肽的新型类似物：鉴定生物活性所需的官能团。
DOI：
10.1021/jm00184a010
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发表时间：
1980
影响因子：
7.3
通讯作者：
Marshall,GR
中科院分区：
文献类型：
--
作者：
Gorin,FA;Balasubramanian,TM;Cicero,TJ;Schwietzer,J;Marshall,GR
Novel tri-and tetrapeptide analogues of enkephalin, in conjunction with earlier structure-activity data, confirm that chemical substituents present in the first and fourth residues of enkephalin are required for in vitro biological activity. A class of arylamino and alkylamino derivatized tripeptides also were found to have signficiant in vitro opioid-like activity indistinguishable from [D-Ala1 2, D-Leu5] enkephalin and morphine.The enkephalins are the smallest members of a family of opioid-like peptides endogenous to the mammalian central nervous system. The in vivo pharmacology of the enkephalins and opiates is complex, and there is growing evidence that these compounds act in vivo at several types of receptors. 1™ 3 In in vitro systems such as the guinea pig ileum, 4 mouse vas deferens, 5 neuroblastoma glioma NG108-15 cell line, 6 and rat brain binding assays, 7 opiates and the enkephalins produce analogous pharmacologic effects which are reversibly blocked by the opiate antag-onist naloxone. These in vitro observations have motivated investigators to compare chemical and conformational similarities between the enkephalins and opiate com-pounds. Numerous conformational studies have proposed receptor-bound conformations for enkephalins whereby these mammalian pentapeptides and plant opiate alkaloids pharmacologically compete for the same in vitro receptors. 8 This article describes novel, conformationally con-strained analogues of enkephalin which are evaluated pharmacologically in the guinea pig ileum and which displace [3H] naloxone in the rat brain binding assay. There is no assurance that the pharmacologic receptors in these two in vitro assays are equivalent, and recent investigation has suggested the existence of separate high affinity “enkephalin receptors” and “morphine (µ) receptors” present in the rat brain binding assay. 2, 3, 9 It
