Profiling protein function with small molecule microarrays.

Nicolas Winssinger; Scott Ficarro; Peter G Schultz; Jennifer L Harris

doi:10.1073/pnas.172286899

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Profiling protein function with small molecule microarrays.

Nicolas Winssinger·Scott Ficarro·Peter G Schultz·Jennifer L Harris

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Abstract

The regulation of protein function through posttranslational modification, local environment, and protein-protein interaction is critical to cellular function. The ability to analyze on a genome-wide scale protein functional activity rather than changes in protein abundance or structure would provide important new insights into complex biological processes. Herein, we report the application of a spatially addressable small molecule microarray to an activity-based profile of proteases in crude cell lysates. The potential of this small molecule-based profiling technology is demonstrated by the detection of caspase activation upon induction of apoptosis, characterization of the activated caspase, and inhibition of the caspase-executed apoptotic phenotype using the small molecule inhibitor identified in the microarray-based profile.

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Amino Acid Sequence Apoptosis Caspase 3 Caspases Cathepsin K Cathepsins Enzyme Inhibitors Gene Expression Profiling Humans Jurkat Cells Oligonucleotide Array Sequence Analysis Phenotype Protein Processing, Post-Translational Proteins Sensitivity and Specificity Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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Nicolas Winssinger, Scott Ficarro, Peter G Schultz, Jennifer L Harris. 2002-08-07. Profiling protein function with small molecule microarrays.. https://doi.org/10.1073/pnas.172286899

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