中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Establishment of kappa opioid receptor agonists pharmacophore with molecular modeling method

文献类型:期刊论文

作者Liu, DX; Tang, Y; Jiang, HL; Chen, KX; Ji, RY
刊名ACTA PHARMACOLOGICA SINICA
出版日期1998-09
卷号19期号:5页码:445-450
关键词molecular mechanics kappa opioid receptors pharmacophore
ISSN号0253-9756
文献子类Article
英文摘要AIM: To build up nonpeptide kappa-opioid receptor agonists pharmacophore. METHODS: Five structurally diverse, highly active nonpeptide kappa-opioid agonists were retrieved from MDL MDDR database. Molecular mechanics method were used to seek out 50 lower energy conformations for each compound. Taking nitrogen atom of pyrrolidine and acyl acetamide as overlay points, 5 agonists were superimposed to each other with their most favorite conformation. From the overlay map, the structure specificity of nonpeptide kappa-opioid receptor agonists were elucidated. RESULTS: According to pharmacophore, the pyrrolidine ring, carbonyl group of acyl acetamide, and the hydrophobic group attached to acyl acetamide were suggested to be the structure-specific moieties of kappa-opioid agonists. Moreover, by comparing kappa(1)-opioid receptor sequence of mouse with other G-protein-coupled receptors, we determined those conserve residues existing on transmembrane regions which might interact with the suggested groups. The carboxyl of Asp138 might interact with N atom of pyrrolidine by forming a hydrogen bond. The hydroxyl of Ser187 and the carbonyl group of kappa-opioid agonists might form another hydrogen bond, which was critical for its kappa selective affinity. The hydrophobic group attached to acyl acetamide might have hydrophobic interaction with aromatic residues of kappa-opioid receptors. CONCLUSION: These kappa agonists pharmacophore were helpful to select specific positions in the lead compounds to be occupied by hydrophobic moieties to limit their ability to across the blood-brain barrier.
WOS关键词PROTEIN-COUPLED RECEPTORS ; BIOLOGICAL EVALUATION ; SIGMA-RECEPTOR ; ACETYLCHOLINE ; LIGANDS
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000075784800013
出版者ACTA PHARMACOLOGICA SINICA
源URL[http://119.78.100.183/handle/2S10ELR8/274807]  
专题药物发现与设计中心
药理学第三研究室
通讯作者Chen, KX
作者单位Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China
推荐引用方式
GB/T 7714
Liu, DX,Tang, Y,Jiang, HL,et al. Establishment of kappa opioid receptor agonists pharmacophore with molecular modeling method[J]. ACTA PHARMACOLOGICA SINICA,1998,19(5):445-450.
APA Liu, DX,Tang, Y,Jiang, HL,Chen, KX,&Ji, RY.(1998).Establishment of kappa opioid receptor agonists pharmacophore with molecular modeling method.ACTA PHARMACOLOGICA SINICA,19(5),445-450.
MLA Liu, DX,et al."Establishment of kappa opioid receptor agonists pharmacophore with molecular modeling method".ACTA PHARMACOLOGICA SINICA 19.5(1998):445-450.

入库方式: OAI收割

来源:上海药物研究所

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