Abstract
Quantitative chemoproteomics has recently emerged as an experimental approach to determine protein interaction profiles of small molecules in a given cell line or tissue. In contrast to standard biochemical and biophysical kinase assays, application of this method to kinase inhibitors determines compound binding to endogenously expressed kinases under conditions approximating the physiological situation with regard to the molecular state of the kinase and presence of required cofactors and regulatory proteins. Using a dose-dependent, competition-based experimental design in combination with quantitative mass spectrometry approaches, such as the use of tandem mass tags (TMT) for isobaric labeling described here, allows to rank-order interactions of inhibitors to kinase by binding affinity.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Fabian, M. A., Biggs, W. H., III, Treiber, D. K., Atteridge, C. E., Azimioara, M. D., Benedetti, M. G., Carter, T. A., Ciceri, P., Edeen, P. T., Floyd, M., Ford, J. M., Galvin, M., Gerlach, J. L., Grotzfeld, R. M., Herrgard, S., Insko, D. E., Insko, M. A., Lai, A. G., Lelias, J. M., Mehta, S. A., Milanov, Z. V., Velasco, A. M., Wodicka, L. M., Patel, H. K., Zarrinkar, P. P., and Lockhart, D. J. (2005) A small molecule-kinase interaction map for clinical kinase inhibitors. Nat.Biotechnol. 23, 329–336.
Vesely, J., Havlicek, L., Strnad, M., Blow, J. J., Donella-Deana, A., Pinna, L., Letham, D. S., Kato, J., Detivaud, L., and Leclerc, S. (1994) Inhibition of cyclin-dependent kinases by purine analogues. Eur.J. Biochem. 224, 771–786.
Hall, S. E. (2006) Chemoproteomics-driven drug discovery: addressing high attrition rates. Drug Discovery Today 11, 495–502.
Rix, U. and Superti-Furga, G. (2009) Target profiling of small molecules by chemical proteomics. Nat. Chem. Biol. 5, 616–624.
Bantscheff, M., Eberhard, D., Abraham, Y., Bastuck, S., Boesche, M., Hobson, S., Mathieson, T., Perrin, J., Raida, M., Rau, C., Reader, V., Sweetman, G., Bauer, A., Bouwmeester, T., Hopf, C., Kruse, U., Neubauer, G., Ramsden, N., Rick, J., Kuster, B., and Drewes, G. (2007) Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors. Nat. Biotechnol. 25, 1035–1044.
Oppermann, F. S., Gnad, F., Olsen, J. V., Hornberger, R., Greff, Z., Keri, G., Mann, M., and Daub, H. (2009) Large-scale proteomics analysis of the human kinome. Mol.Cell Proteomics. 8, 1751–1764.
Graves, P. R., Kwiek, J. J., Fadden, P., Ray, R., Hardeman, K., Coley, A. M., Foley, M., and Haystead, T. A. (2002) Discovery of novel targets of quinoline drugs in the human purine binding proteome. Mol.Pharmacol. 62, 1364–1372.
Ong, S. E., Schenone, M., Margolin, A. A., Li, X. Y., Do, K., Doud, M. K., Mani, D. R., Kuai, L., Wang, X., Wood, J. L., Tolliday, N. J., Koehler, A. N., Marcaurelle, L. A., Golub, T. R., Gould, R. J., Schreiber, S. L., and Carr, S. A. (2009) Identifying the proteins to which small-Âmolecule probes and drugs bind in cells. Proc. Natl. Acad. Sci. USA 106,4617–4622.
Sharma, K., Weber, C., Bairlein, M., Greff, Z., Keri, G., Cox, J., Olsen, J. V., and Daub, H. (2009) Proteomics strategy for quantitative protein interaction profiling in cell extracts. Nat. Methods 6, 741–744.
Garcia-Echeverria, C., Kanazawa, T., Kawahara, E., Masuya, K., Matsuura, N., Miyake, T., Ohmori, O., and Umemura, I. (2004) Preparation of novel 2,4-di(phenylamino)pyrimidines useful in the treatment of neoplastic diseases, inflammatory and immune system disorders. PCT Int. Appl. WO2004080980 A1 20040923.
Baenteli, R., Zenke, G., Cooke, N. G., Duthaler, R., Thoma, G., Von Matt, A., Honda, T., Matsuura, N., Nonomura, K., Ohmori, O., Umemura, I., Hinterding, K., and Papageorgiou, C. (2003) Pyrimidine derivatives. PCT Int. Appl. WO 2003078404 A1 20030925.
Duthaler, R., Gerspacher, M., Holzer, P., Streiff, M., Thoma, G., Waelchli, R., and Zerwes, HG. (2007) Preparation of 2,4-di(arylamino)-pyrimidine-5-carboxamides as JAK kinases inhibitors. PCT Int. Appl. WO 2008009458 A1 20080124.
Garcia-Echeverria, C., Kanazawa, T., Kawahara, E., Masuya, K., Matsuura, N., Miyake, T., Ohmori, O., Umemura, I., Steensma, R., Chopiuk, G., Jiang, J., Wan, Y., Zhang, Q., Gray, N. S., and Karanewsky, D. (2004) Preparation of 2,4-pyrimidinediamines useful in the treatment of neoplastic diseases, inflammatory and immune system disorders. PCT Int. Appl. WO2005016894 A1 20050224.
Argade, A., Singh, R., Li, H., Carroll, D., and Catalano, S. (2004) 2,4-pyrimidinediamine compounds and uses as antiproliferative agents. PCT Int. Appl. WO 2005013996 A2 20050217.
Bantscheff, M., Boesche, M., Eberhard, D., Matthieson, T., Sweetman, G., and Kuster, B. (2008) Robust and sensitive iTRAQ quantification on an LTQ Orbitrap mass spectrometer. Mol.Cell Proteomics. 7, 1702–1713.
Jaffe, J. D., Keshishian, H., Chang, B., Addona, T. A., Gillette, M. A., and Carr, S. A. (2008) Accurate inclusion mass screening: a bridge from unbiased discovery to targeted assay development for biomarker verification. Mol.Cell Proteomics. 7, 1952–1962.
Acknowledgments
We thank Heather Contant and Lindsay Nolitt for expert technical assistance and John Damask and Ioannis Moutsatsos for their crucial role in building the data processing and analysis environment.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Schirle, M. et al. (2012). Kinase Inhibitor Profiling Using Chemoproteomics. In: Kuster, B. (eds) Kinase Inhibitors. Methods in Molecular Biology, vol 795. Humana Press. https://doi.org/10.1007/978-1-61779-337-0_11
Download citation
DOI: https://doi.org/10.1007/978-1-61779-337-0_11
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-336-3
Online ISBN: 978-1-61779-337-0
eBook Packages: Springer Protocols