期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 85, 期 -, 页码 818-829出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2014.07.077
关键词
Salvinorin A and B; Michael acceptor-type ligands; Kappa, delta and mu opioid receptors; Molecular modeling
资金
- NIH [R01 DA017204]
- NIMH Psychoactive Drug Screening Program (PDSP) [HHSN-271-2013-00017-C]
- University of North Carolina Chapel Hill [NC 27599]
The neoclerodane diterpenoid salvinorin A is a major secondary metabolite isolated from the psychoactive plant Salvia divinorum. Salvinorin A has been shown to have high affinity and selectivity for the K-opioid receptor (KOR). To study the ligand-receptor interactions that occur between salvinorin A and the KOR, a new series of salvinorin A derivatives bearing potentially reactive Michael acceptor functional groups at C-2 was synthesized and used to probe the salvinorin A binding site. The K-, delta-, and mu-opioid receptor (KOR, DOR and MOR, respectively) binding affinities and KOR efficacies were measured for the new compounds. Although none showed wash-resistant irreversible binding, most of them showed high affinity for the KOR, and some exhibited dual affinity to KOR and MOR. Molecular modeling techniques based on the recently-determined crystal structure of the KOR combined with results from mutagenesis studies, competitive binding, functional assays and structure-activity relationships, and previous salvinorin A-KOR interaction models were used to identify putative interaction modes of the new compounds with the KOR and MOR. (C) 2014 Elsevier Masson SAS. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据