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
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

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