You are here

Proceedings of the National Academy of Sciences of the United States of America DOI:10.1073/pnas.0900191106

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

Publication TypeJournal Article
Year of Publication2009
AuthorsOng, SE, Schenone, M, Margolin, AA, Li, X, Do, K, Doud, MK, Mani, DR, Kuai, L, Wang, X, Wood, JL, Tolliday, NJ, Koehler, AN, Marcaurelle, LA, Golub, TR, Gould, RJ, Schreiber, SL, Carr, SA
JournalProceedings of the National Academy of Sciences of the United States of America
Date Published2009/03/24

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.


Recent Broad Publications

No results found