Linked Life Data

19615965

Source:http://linkedlifedata.com/resource/pubmed/id/19615965

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-8-31
pubmed:abstractText
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 microm 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1096-0309
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
394
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
62-7
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Capillary electrophoresis for screening of 20S proteasome inhibitors.
pubmed:affiliation
Department of Pharmaceutical Analysis, School of Pharmaceutical Science, Peking University, Beijing 100191, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't