EVIDENCE OF A PEPTIDE BACKBONE CONTRIBUTION TOWARD SELECTIVE RECEPTOR RECOGNITION FOR LEUCINE ENKEPHALIN THIOAMIDE ANALOGS
EVIDENCE OF A PEPTIDE BACKBONE CONTRIBUTION TOWARD SELECTIVE RECEPTOR RECOGNITION FOR LEUCINE ENKEPHALIN THIOAMIDE ANALOGS
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DOI：
10.1016/0006-291x(84)91449-9
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发表时间：
1984-01-01
影响因子：
3.1
通讯作者：
LAWESSON, SO
中科院分区：
文献类型：
--
作者：
CLAUSEN, K;SPATOLA, AF;LAWESSON, SO
在μ-l中测定一系列在主链的不同位置含有硫代酰胺键代替肽键的亮氨酸脑啡肽类似物的体外阿片样物质活性[豚鼠回肠，小鼠输精管]。和δ-受体选择性生物测定和结合测定。在1-2位的硫代酰胺取代产生无活性化合物，而在2-3和4-5位的相同修饰产生效力增强。最有趣的是，2-3修饰的类似物显示出对δ-的3-5倍高的偏好。超过μ-受体比天然亮氨酸脑啡肽。微妙的骨架修饰可以对生物活性肽的受体亲和力和选择性产生深远的影响。
The in vitro opioid activities [guinea pig ileum, mouse vas deferens] of a series of leucine enkephalin analogs containing a thioamide linkage in place of the peptide bond at various positions of the backbone were determined in .mu.- and .delta.-receptor-selective biossays and binding assays. Thioamide substitution in the 1-2 position resulted in a inactive compound, whereas the same modification in the 2-3 and 4-5 position produced potency enhancement. Most interestingly, the 2-3 modified analog showed a 3-5 times higher preference for .delta.- over .mu.-receptors than natural leucine enkephalin. Subtle backbone modifications can have a profound effect on receptor affinity and selectivity of biologically active peptides.