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        Small Molecule Protein Interaction Profiling with Functional Protein Microarrays

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        Small molecules possess the ability to interact with proteins and perturb their specific functions, a property that has been exploited for numerous research applications and to produce therapeutic agents in disease treatment. However, commonly utilized mass spectrometry-based approaches for identifying the target proteins for a small molecule have a number of limitations, particularly in terms of throughput and time and resource consumption. In addition, current technologies lack a mechanism to broadly assess the selectivity profile of the small molecule, which may be important for understanding off-target effects of the compound. Protein microarray technology has emerged as a powerful tool in the systems biology arsenal. Here, we describe how protein microarray technology can be applied to the study of small molecule protein interactions, with sensitivity sufficient to detect interactions with low μM affinity. These assays are highly reproducible, sensitive, and scalable, and provide an enabling technology for small molecule selectivity profiling in the context of drug development.
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