Structure-Based Optimization of Multifunctional Agonists for Opioid and Neuropeptide FF Receptors with Potent Nontolerance Forming Analgesic Activities

doi:10.1021/acs.jmedchem.6b01181

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	Structure-Based Optimization of Multifunctional Agonists for Opioid and Neuropeptide FF Receptors with Potent Nontolerance Forming Analgesic Activities
	Wang, ZL; Pan, JX; Song, JJ; Tang, HH; Yu, HP; Li, XH; Li, N; Zhang, T; Zhang, R; Zhang, MN
刊名	JOURNAL OF MEDICINAL CHEMISTRY
	2016-11-24
卷号	59 期号:22 页码:10198-10208
ISSN号	0022-2623
DOI	10.1021/acs.jmedchem.6b01181
文献子类	Article
英文摘要	The opioid and neuropeptide FF pharmacophore-containing chimeric peptide 0 (BN-9) was recently developed and produced potent nontolerance forming analgesia. In this study, 11 analogues of 0 were designed and synthesized. An in vitro cAMP assay demonstrated that these analogues behaved as multifunctional agonists at both opioid and NPFF receptors. In mouse tail-flick test, most of the analogues produced potent nontolerance forming antinociception. Notably, 11 (DN-9) was 33-fold more potent than 0 at analgesic effects, which was mediated by mu- and kappa-opioid receptors. In addition, 11 also produced powerful analgesic effects in the formalin pain and CFA-induced chronic inflammatory pain models. Strikingly, following its repeated administration for 6 days, 11 did not produce antinociceptive tolerance in the tail flick test and CFA-induced pain model. The present work indicates that it is reasonable to design multifunctional peptide ligands for opioid and NPFF receptors in a single molecule producing effective nontolerance forming antinociception.
学科主题	Pharmacology & Pharmacy
出版地	WASHINGTON
资助项目	国家自然科学基金项目 ; 新世纪优秀人才支持计划 ; 长江学者和创新团队发展计划 ; 中央高校基本科研业务费专项资金
项目编号	National Natural Science Foundation of China [81273355, 81473095] ; Program for New Century Excellent Talents in University [NCET-13-0257] ; Program for Changjiang Scholars and Innovative Research Team in University [IRT_15R27] ; Fundamental Research Funds for the Central Universities [lzujbky-2016-58]
语种	英语
WOS记录号	WOS:000388913200013
资助机构	NSFC ; MOE ; LZU
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/188718]
专题	基础医学院_期刊论文
通讯作者	Fang, Q; Wang, R (reprint author), Lanzhou Univ, Sch Basic Med Sci, Key Lab Preclin Study New Drugs Gansu Prov, 199 Donggang West Rd, Lanzhou 730000, Peoples R China.
推荐引用方式 GB/T 7714	Wang, ZL,Pan, JX,Song, JJ,et al. Structure-Based Optimization of Multifunctional Agonists for Opioid and Neuropeptide FF Receptors with Potent Nontolerance Forming Analgesic Activities[J]. JOURNAL OF MEDICINAL CHEMISTRY,2016,59(22):10198-10208.
APA	Wang, ZL.,Pan, JX.,Song, JJ.,Tang, HH.,Yu, HP.,...&Wang, R .(2016).Structure-Based Optimization of Multifunctional Agonists for Opioid and Neuropeptide FF Receptors with Potent Nontolerance Forming Analgesic Activities.JOURNAL OF MEDICINAL CHEMISTRY,59(22),10198-10208.
MLA	Wang, ZL,et al."Structure-Based Optimization of Multifunctional Agonists for Opioid and Neuropeptide FF Receptors with Potent Nontolerance Forming Analgesic Activities".JOURNAL OF MEDICINAL CHEMISTRY 59.22(2016):10198-10208.