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PNAS 99 (17): 11139-11144

Copyright © 2002 by the National Academy of Sciences.


Profiling protein function with small molecule microarrays

Nicolas Winssinger*,{dagger}, Scott Ficarro*, Peter G. Schultz*,{dagger},{ddagger}, and Jennifer L. Harris*,{ddagger}

*Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121; and {dagger}Department of Chemistry, The Scripps Research Institute, and The Skaggs institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037

Received for publication 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.

{ddagger} To whom reprint requests may be addressed. E-mail: harris{at} or schultz{at}

Edited by Christopher T. Walsh, Harvard Medical School, Boston, MA, and approved June 18, 2002

This paper was submitted directly (Track II) to the PNAS office.

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