北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学药学院  > 药物化学系  > 期刊论文
学科主题: 药学
题名:
Synthesis and preliminary evaluation of peptidomimetic inhibitors of human beta-secretase
作者: Niu, Yan1; Wang, Yuehua2; Zou, Xiaomin1; Yang, Xiaoming1; Ma, Chao1; Lue, Yang1; Zhou, Bo1; Yuan, Yue1; Du, Guanhua2; Xu, Ping1
关键词: beta-Secretase inhibitor ; Hydroxyethylene isostere ; CADD ; Peptidomimetic ; Synthesis
刊名: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
发表日期: 2010-05-01
DOI: 10.1016/j.ejmech.2010.01.044
卷: 45, 期:5, 页:2089-2094
收录类别: SCI ; IC
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Medicinal
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: ALZHEIMERS-DISEASE ; POTENT INHIBITORS ; PROTEASE ; DESIGN ; BACE
英文摘要:

Based on the structure of OM99-2 and the X-ray crystal structure of its complex with beta-secretase, a series of compounds containing the Leu*Ala hydroxyethylene isostere as a scissile bond substitution were designed. 31 compounds were synthesized and their beta-secretase inhibition activities were measured. It was found that isobutyl group was a better R(3) substitution as C-terminus in our target compounds, and 4-nitrobenzyl group was the best R(2) side chain. With the aid of molecular modeling, the binding modes of compounds 9 and 22 with beta-secretase were compared. The result revealed a stronger bonding mode of 22 than 9. This explored that the optimal length of this series of peptidomimetic inhibitors was P3-P2′. The molecular weights of compounds with this length are around 600. (C) 2010 Elsevier Masson SAS. All rights reserved.

语种: 英语
所属项目编号: 30772650 ; 20772008
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000276695200051
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52030
Appears in Collections:北京大学药学院_药物化学系_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Peking Univ, Sch Pharmaceut Sci, Dept Med Chem, Beijing 100191, Peoples R China
2.Chinese Acad Med Sci, Inst Mat Med, Beijing 100050, Peoples R China

Recommended Citation:
Niu, Yan,Wang, Yuehua,Zou, Xiaomin,et al. Synthesis and preliminary evaluation of peptidomimetic inhibitors of human beta-secretase[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2010,45(5):2089-2094.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Niu, Yan]'s Articles
[Wang, Yuehua]'s Articles
[Zou, Xiaomin]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Niu, Yan]‘s Articles
[Wang, Yuehua]‘s Articles
[Zou, Xiaomin]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace