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学科主题: 药学
题名:
3D-QSAR and docking studies on 2-arylbenzoxazole and linker-Y transthyretin amyloidogenesis inhibitors
作者: Zhao LiJun1; Zhang LiangRen2; Lei Ming1
关键词: transthyretin ; 3D-QSAR ; 2-arylbenzoxazoles ; linker-Y ; docking ; binding mode
刊名: SCIENCE CHINA-CHEMISTRY
发表日期: 2013-11-01
DOI: 10.1007/s11426-013-4894-9
卷: 56, 期:11, 页:1550-1563
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary
研究领域[WOS]: Chemistry
关键词[WOS]: AMYLOID FIBRIL INHIBITORS ; LIVER-TRANSPLANTATION ; SUBSTRUCTURE COMMON ; MOLECULAR DOCKING ; RATIONAL DESIGN ; SHEET STRUCTURE ; NATIVE-STATE ; POTENT ; BINDING ; POLYNEUROPATHY
英文摘要:

Transthyretin (TTR), a plasma protein with a tetramer structure, could form amyloid fibril associated with several human diseases through the dissociation of tetramer and the misfolding of monomer. These amyloidogenesis can be inhibited by small molecules which bind to the central channel of TTR. A number of small molecules like 2-arylbenzoxazoles (ABZ) analogues are proposed as promising therapeutic strategy to treat amyloidosis. In this work, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) three-dimensional quantitative structure-activity relationship (3D-QSAR) and docking studies were performed on series of 2-arylbenzoxazoles (ABZ) and linker-Y analogues to investigate the inhibitory activities of TTR amyloidogenesis at atomic level. Significant correlation coefficients for ABZ series (CoMFA, r (2) = 0.877, q (2) = 0.431; CoMSIA, r (2) = 0.836, q (2) = 0.447) and those for linker-Y series (CoMFA, r (2) = 0.828, q (2) = 0.522; CoMSIA, r (2) = 0.800, q (2) = 0.493) were obtained, and the generated models were validated using test sets. In addition, docking studies on 6 compounds binding to TTR were performed to analyze the forward or reverse binding mode and interactions between molecules and TTR. These results from 3D-QSAR and docking studies have great significance for designing novel TTR amyloidogenesis inhibitors in the future.

语种: 英语
所属项目编号: 21072018 ; ZY1213 ; K20120202
项目资助者: National Natural Science Foundation of China ; Fundamental Research Funds for the Central Universities ; Foundation of State Key Laboratory of Natural and Biomimetic Drugs
WOS记录号: WOS:000326327500009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52313
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Beijing Univ Chem Technol, Coll Sci, Inst Mat Med, State Key Lab Chem Resource Engn, Beijing 100029, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100083, Peoples R China

Recommended Citation:
Zhao LiJun,Zhang LiangRen,Lei Ming. 3D-QSAR and docking studies on 2-arylbenzoxazole and linker-Y transthyretin amyloidogenesis inhibitors[J]. SCIENCE CHINA-CHEMISTRY,2013,56(11):1550-1563.
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