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学科主题: 药学
题名:
Capillary electrophoresis for screening of 20S proteasome inhibitors
作者: Chen, Wenjing1; Mou, Ke2; Xu, Bo3; Ling, Xiaomei1; Cui, Jingrong3; Xu, Ping2
关键词: 20S proteasome ; Enzyme inhibitor ; MG132 ; MG115 ; Peptidyl vinyl ester ; Capillary electrophoresis
刊名: ANALYTICAL BIOCHEMISTRY
发表日期: 2009-11-01
DOI: 10.1016/j.ab.2009.07.020
卷: 394, 期:1, 页:62-67
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemical Research Methods ; Biochemistry & Molecular Biology ; Chemistry, Analytical
研究领域[WOS]: Biochemistry & Molecular Biology ; Chemistry
关键词[WOS]: MULTICATALYTIC PROTEINASE COMPLEX ; CHYMOTRYPSIN-LIKE ACTIVITY ; FLUORESCENCE DETECTION ; S PROTEASOME ; BORONIC ACID ; DEGRADATION ; ASSAY ; METABOLISM ; SUBSTRATE ; ALDEHYDES
英文摘要:

A method for studying 20S proteasome inhibitors by capillary electrophoresis (CE) has been developed. Proteasome plays a fundamental role in degrading key regulatory proteins. The 20S proteasome can degrade intrinsically disordered proteins in an ATP-independent manner without additional "helper" molecules. The discovery of new proteasome inhibitors with little or no toxicity is highly desirable in anticancer therapy. In this study, the inhibitory effects of MG132 and MG115 on the 20S proteasome were evaluated by CE for the first time. The optimized CE conditions were as follows: fused-silica capillary of 30 cm effective length and 75 mu m internal diameter, pressure injection of 0.5 psi for 5 s, 50 mM Hepes buffer (pH 7.6) with 2% dimethyl sulfoxide, constant voltage of 20 kV, and detection wavelength at 340 nm. Also, the new method was used to study the inhibitory effects of 30 novel peptidyl vinyl ester derivatives of MG132. The 50% inhibition concentrations (IC(50) values) of MG132 and MG115 were 40.0 and 84.7 nM, respectively. Two new compounds, XP32 and XP35, showed considerable inhibitory effects on the 20S proteasome. When the concentrations of them were fixed at 172 nM, their inhibition rates were 36.2% and 29.1%, respectively. The results showed that the CE method was powerful, sensitive, and fast and required little sample. It could be employed as one of the reliable drug screening methods for 20S proteasome inhibitors. (C) 2009 Elsevier Inc. 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:000272883900009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52541
Appears in Collections:北京大学药学院_化学生物学系_期刊论文

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作者单位: 1.Peking Univ, Dept Pharmaceut Anal, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
2.Peking Univ, Dept Med Chem, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
3.Peking Univ, Natl Res Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

Recommended Citation:
Chen, Wenjing,Mou, Ke,Xu, Bo,et al. Capillary electrophoresis for screening of 20S proteasome inhibitors[J]. ANALYTICAL BIOCHEMISTRY,2009,394(1):62-67.
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