Abstract
Background: Target identification is a critical step in elucidating the mechanism of action (MoA) for bioactive compounds. For target-based and phenotypic drug discovery pipelines, extensive potential target knowledge for a lead compound provides essential insights that enable potency and selectivity optimization. The tedious process of target deconvolution for a compound often necessitates a plethora of biochemical and biophysical techniques. To expand the toolbox of unbiased target ID approaches, we developed a drug target deconvolution workflow combining limited proteolysis with quantitative mass spectrometry (LiP-MS) that exploits the drug binding phenomena of protein structural alterations and steric hindrance.
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