检索结果-南通市图书馆

Construction of a small peptide library related to inhibitor om99-2 and its structure-activity relationship to β-secretase

引用

Acta Pharmacologica Sinica 2006年第12期27卷 1586-1593页

作者： Bin HU Bing XIONG Bei-ying QIU Xin LI Hai-ping YU Kun XIAO Xin WANG Jia LI Jing-kang SHEN~2 State Key Laboratory of Drug Research and National Center for Drug Screening,Shanghai Institute of Materia Medica,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 201203,China State Key Laboratory of Drug Research and National Center for Drug Screening Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China

Aim:To develop probes for detecting the binding specificity between β-secretaseand substrate,and provide reliable biological activity data for further researchingencircling substrate-based ***:To prepare the inhibitors,thehydroxyethylene(HE)segment including P1and P1′ was synthesized after multi-step reactions;the combination of all segments was then completed through solidphase *** human β-secretase ectodomain(amino acid resi-dues 1-460)was expressed as a secreted protein with a C-terminal His tag in insectcells using baculovirus infection,and all compounds were evaluated in thisβ-secretase enzyme *** order to understand the interaction in detail,the theoretical methods,namely molecular dynamics(MD)simulation and mo-lecular mechanics-generalized-born surface area(MM-GBSA)analysis,were per-formed on the complex of β-secretase and om99-2 to obtain the geometrical andenergetical ***:We designed and constructed a positional scan-ning combinatorial library including 16 compounds;all members of the librarywere synthesized based on HE dipeptide ***-activity relationshipstudies at the P4-P1and P1′-P4′ positions led to the discoveries of P and P’sidesbinding specificity and potent inhibitors 14,18,and *** binding free energyon the whole system and every residue were compared to the biological ***:The removal of P4′ yielded inhibitor 22(A3*B2)with highpotency;further truncation of P3′ gave inhibitor 18(A3*B1)with equal activity,implying that the right side of the inhibitors play a less important role and could beeasily simplified,while change on the P side may cause substantial results.

关键词： β-secretase hydroxyethylene om99-2 Alzheimer’s disease structure-activity relationship

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

语言

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

语言

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：