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PMID: 12167675 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Profiling protein function with small molecule microarrays.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 17 ·2002-08-20 ·Pages 11139-44

Winssinger N, Ficarro S, Schultz PG, Harris JL

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.

MeSH Terms
Amino Acid Sequence Apoptosis Caspase 3 Caspases/metabolism Cathepsin K Cathepsins/antagonists & inhibitors Enzyme Inhibitors/chemistry Gene Expression Profiling Humans Jurkat Cells Oligonucleotide Array Sequence Analysis Phenotype Protein Processing, Post-Translational Proteins/genetics,metabolism Sensitivity and Specificity
Chemicals
Enzyme Inhibitors Proteins Cathepsins CASP3 protein, human Caspase 3 Caspases CTSK protein, human Cathepsin K
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Winssinger Nicolas
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
Ficarro Scott
Schultz Peter G
Harris Jennifer L
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.172286899
Published
2002-08-20
Epub
2002-00-07
Pages
11139-44
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC123223
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.172286899 PMC Full Text View journal details
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