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Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4617-22. doi: 10.1073/pnas.0900191106. Epub 2009 Mar 2.

Identifying the proteins to which small-molecule probes and drugs bind in cells.

Author information

  • 1Proteomics Platform, The Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. song@broad.mit.edu

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.

PMID:
19255428
[PubMed - indexed for MEDLINE]
PMCID:
PMC2649954
Free PMC Article

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