Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

PNAS 99 (17): 11139-11144

Copyright © 2002 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / BIOCHEMISTRY

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}gnf.org or schultz{at}scripps.edu.

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.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A trap-and-release integrated microfluidic system for dynamic microarray applications.
W.-H. Tan and S. Takeuchi (2007)
PNAS 104, 1146-1151
   Abstract »    Full Text »    PDF »
Protein "fingerprinting" in complex mixtures with peptoid microarrays.
M. M. Reddy and T. Kodadek (2005)
PNAS 102, 12672-12677
   Abstract »    Full Text »    PDF »
From The Cover: Microarrays of small molecules embedded in biodegradable polymers for use in mammalian cell-based screens.
S. N. Bailey, D. M. Sabatini, and B. R. Stockwell (2004)
PNAS 101, 16144-16149
   Abstract »    Full Text »    PDF »
The Stanford Microarray Database: data access and quality assessment tools.
J. Gollub, C. A. Ball, G. Binkley, J. Demeter, D. B. Finkelstein, J. M. Hebert, T. Hernandez-Boussard, H. Jin, M. Kaloper, J. C. Matese, et al. (2003)
Nucleic Acids Res. 31, 94-96
   Abstract »    Full Text »    PDF »
The History of Nutrition: Malnutrition, Infection and Immunity.
G. T. Keusch (2003)
J. Nutr. 133, 336S-340
   Abstract »    Full Text »    PDF »
Chemical Strategies for Functional Proteomics.
G. C. Adam, E. J. Sorensen, and B. F. Cravatt (2002)
Mol. Cell. Proteomics 1, 781-790
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882