Constance J. Glover;Karen Hite;Renee DeLosh;Dominic A. Scudiero;Matthew J. Fivash;Lindsey R. Smith;Robert J. Fisher;Jia Wei Wu;一公 施;Rachael A. Kipp;George L. McLendon;Edward A. Sausville;Robert H. Shoemaker
National Institutes of Health;SAIC;Princeton University;China Association for Science and Technology
发表时间:2003-9-15
期 刊:Analytical Biochemistry
语 言:English
U R L: http://www.scopus.com/inward/record.url?scp=12444295103&partnerID=8YFLogxK
Resistance to apoptosis is afforded by inhibitor of apoptosis proteins (IAPs) which bind to and inhibit the caspases responsible for cleavage of substrates leading to apoptotic cell death. Smac (or DIABLO), a proapoptotic protein released from the mitochondrial intermembrane space into the cytosol, promotes apoptosis by binding to IAPs, thus reversing their inhibitory effects on caspases. We have developed a high-throughput fluorescence polarization assay utilizing a fluorescein-labeled peptide similar to the "IAP binding" domain of Smac N terminus complexed with the BIR3 domain of X-linked IAP (XIAP) to identify small-molecule mimics of the action of Smac. The IC50s of peptides and a tetrapeptidomimetic homologous to the N terminus of Smac demonstrated the specificity and utility of this assay. We have screened the National Cancer Institute "Training Set" of 230 compounds, with well-defined biological actions, and the "Diversity Set" of 2000 chemically diverse structures for compounds which significantly reduced fluorescence polarization. Highly fluorescing or fluorescence-quenching compounds (false positives) were distinguished from those which interfered with Smac peptide binding to the XIAP-BIR3 in a dose-dependent manner (true positives). This robust assay offers potential for high-throughput screening discovery of novel compounds simulating the action of Smac/DIABLO.
化合物
医学与生命科学
Scopus度量
年份 | CiteScore | SJR | SNIP |
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1996 | |||
1997 | |||
1998 | |||
1999 | 1.157 | 0.974 | |
2000 | 1.056 | 0.973 | |
2001 | 0.906 | 0.863 | |
2002 | 1.039 | 0.97 | |
2003 | 1.057 | 0.964 | |
2004 | 1.007 | 0.961 | |
2005 | 1.105 | 0.936 | |
2006 | 1.097 | 0.944 | |
2007 | 1.149 | 0.968 | |
2008 | 1.097 | 0.914 | |
2009 | 1.046 | 0.973 | |
2010 | 1.055 | 0.931 | |
2011 | 4.5 | 0.951 | 0.963 |
2012 | 4.6 | 0.945 | 0.956 |
2013 | 4.5 | 0.857 | 0.926 |
2014 | 4.5 | 0.825 | 0.83 |
2015 | 4.4 | 0.729 | 0.784 |
2016 | 4.5 | 0.719 | 0.745 |
2017 | 4.3 | 0.633 | 0.643 |
2018 | 4.2 | 0.587 | 0.664 |
2019 | 4.8 | 0.632 | 0.816 |
2020 | 4.7 |
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