Profiling protein function with small molecule microarrays
- *Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121; and †Department of Chemistry, The Scripps Research Institute, and The Skaggs institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037
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Edited by Christopher T. Walsh, Harvard Medical School, Boston, MA, and approved June 18, 2002 (received for review May 13, 2002)
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.
Footnotes
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↵ ‡ To whom reprint requests may be addressed. E-mail: harris{at}gnf.org or schultz{at}scripps.edu.
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This paper was submitted directly (Track II) to the PNAS office.
- Abbreviations:
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PNA, peptide nucleic acid
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- Copyright © 2002, The National Academy of Sciences
