Abstract
The combination of photoaffinity labeling (PAL) and quantitative chemoproteomics enables the comprehensive, unbiased determination of protein interaction profiles to support target identification of bioactive small molecules. This approach is amenable to cells in culture and compatible with pharmacologically relevant transmembrane target classes like G-protein coupled receptors and ions channels which have been notoriously hard to access by conventional chemoproteomics approaches. Here, we describe a strategy that combines PAL probe titration and competition with excess parental compounds with the goal of enabling the identification of specific interactors as well as assessing the functional relevance of a binding event for the phenotype under investigation.
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Acknowledgments
We thank John Damask and Stephen Marshall for their crucial role in building the data processing and analysis environment.
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Thomas, J.R., Brittain, S.M., Lipps, J., Llamas, L., Jain, R.K., Schirle, M. (2017). A Photoaffinity Labeling-Based Chemoproteomics Strategy for Unbiased Target Deconvolution of Small Molecule Drug Candidates. In: Lazar, I., Kontoyianni, M., Lazar, A. (eds) Proteomics for Drug Discovery. Methods in Molecular Biology, vol 1647. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7201-2_1
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DOI: https://doi.org/10.1007/978-1-4939-7201-2_1
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