Identifying the proteins to which small-molecule probes and drugs bind in cells
Name
Ong-2009-Identifying the prot.pdf
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752.41 KB
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Author(s)
Ong, Shao-En
Schenone, Monica
Margolin, Adam A.
Li, Xiaoyu
Do, Kathy
Doud, Mary Kathryn
Mani, D. R.
Kuai, Letian
Wang, Xiang
Wood, John L.
Date Issued
March 2009
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences
Citation
Ong, Shao-En et al. “Identifying the proteins to which small-molecule probes and drugs bind in cells.” Proceedings of the National Academy of Sciences 106.12 (2009): 4617-4622.
Version
Final published version
Abstract
Most small-molecule probes and drugs alter cell circuitry by interacting with 1 or more proteins. A complete understanding of the interacting proteins and their associated protein complexes, whether the compounds are discovered by cell-based phenotypic or target-based screens, is extremely rare. Such a capability is expected to be highly illuminating—providing strong clues to the mechanisms used by small-molecules to achieve their recognized actions and suggesting potential unrecognized actions. We describe a powerful method combining quantitative proteomics (SILAC) with affinity enrichment to provide unbiased, robust and comprehensive identification of the proteins that bind to small-molecule probes and drugs. The method is scalable and general, requiring little optimization across different compound classes, and has already had a transformative effect on our studies of small-molecule probes. Here, we describe in full detail the application of the method to identify targets of kinase inhibitors and immunophilin binders.
MIT Department
Broad Institute of MIT and Harvard
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
http://dx.doi.org/10.1073/pnas.0900191106
