Tandem mass tag-enabled multiplexed chemoproteomics workflows for drug discovery

Chemoproteomics technologies support drug discovery by using tool molecules to study regulatory processes and their dysregulation in disease and by characterizing the targets and mechanisms by which drugs and drug candidates show efficacy or elicit adverse reactions. Isobaric mass tags such as the TMT/TMTpro reagents enable the multiplexed mass spectrometric analysis of up to 18 samples und thus facilitate the study of concentration and time-dependent changes with almost no missing data points and excellent precision. In this presentation we outline how tandem mass tag-enabled multiplexed chemoproteomics workflows allow measuring small molecule binding to endogenously expressed protein complexes in cell extracts and live cells; we demonstrate how global measurements of protein thermal stability can inform drug targets, selectivity and mechanism of action with spatial resolution and we measure how targeted degraders alter synthesis and degradation rates across the proteome.