Appaso M. Jadhav

Abstract Posttranslational modifications (PTMs) vastly expand the diversity of the human proteome, dynamically reshaping protein activity, interactions and localization in response to environmental, pharmacologic and disease-associated cues. However, their proteome-wide impact on small-molecule recognition—and, thus, druggability—remains largely unexplored. Here we present a chemical proteomic strategy to delineate how PTM states remodel protein ligandability in human cells.

Abstract Targeted protein degradation (TPD) is an emergent therapeutic strategy with the potential to circumvent challenges associated with targets unamenable to conventional pharmacological inhibition. Among TPD approaches, Proteolysis Targeting Chimeras (PROTACs) have shown marked advancement with numerous candidates in clinical development. Despite their potential, most PROTACs utilize advanced small molecule inhibitors, inherently limiting the scope of this approach.