Biocatalytic- and Chemoproteomic-Guided Discovery of a PHGDH Inhibitor from Chemoenzymatic-Promoted DNA-Encoded Libraries Selection Platform.

ABSTRACT: DNA-encoded libraries (DELs) have emerged as an effective and efficient selection strategy for lead compound discovery in academia and industry over the past few decades. Despite recent advancements in this field, DEL remains limited by sensitive DNA-based constructs, particularly with low selection success rates resulting from the random selection of targets. Here, we describe a chemoenzymatic on-DNA reaction for DEL syntheses and develop a chemoproteomic-guided DEL selection platform. This platform, termed FF tags-biocatDEL, integrates DEL technology, chemoenzymatic synthesis, and fully functionalized (FF) chemical tags to match DELs with selection targets, even with limited information about ligandable hotspots. Using two diazirine-based FF indole probes, we comprehensively surveyed bin

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12679622 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature