N-terminal alkylated derivatives of [D-Pro10]dynorphin A-(1-11) are highly selective for kappa-opioid receptors.
N-terminal alkylated derivatives of [D-Pro10]dynorphin A-(1-11) are highly selective for kappa-opioid receptors.
复制标题
[D-Pro10]强啡肽 A-(1-11) N 端烷基化衍生物对 κ 阿片受体具有高度选择性。
DOI：
10.1021/jm00102a019
复制
发表时间：
1992
影响因子：
7.3
通讯作者：
Aldrich,JV
中科院分区：
文献类型：
--
作者：
Choi,H;Murray,TF;DeLander,GE;Caldwell,V;Aldrich,JV
Dynorphin A (Dyn A), one of the endogenous opioid peptides, preferentially interacts with «-opioid receptors1 and is therefore thought to be an endogenous ligand for this opioid receptor type. Since it also exhibits good affinity for µ-and-opioid binding sites, 1 2 various structural modifications have been made to Dyn A in attempts to identify analogues with enhanced selectivity for «-receptors. Such analogues could then be used as tools to better understand the physiological effects of Dyn A mediated by «-receptors. It has been reported that the introduction of lV, IV-diallyltyrosine at position 1 of [D-Pro10] Dyn A-(l-11) endows thepeptide with antagonist activity. NJV-Diallyl-[D-Pro10] Dyn A-(l-ll), however, exhibits low selectivity for «-receptors and is only a weak antagonist. 3 As part of our efforts to develop selective and potent antagonists for «-receptors, we synthesized N-monoalkyl-ated [d-10] Dyn A-(l-ll) analogues in orderto examine whether the second alkyl group was necessary for antag-onist activity. Surprisingly, the introduction of an N-monoalkylated tyrosine at position 1 provided marked selectivity for «-opioidbinding sites. The agonist potency of these peptides in the guinea pig ileum (GPI) assay varied depending on the N-terminal substituents.
