Expedited mapping of the ligandable proteome using fully functionalized enantiomeric probe pairs.

ABSTRACT: A fundamental challenge in chemical biology and medicine is to understand and expand the fraction of the human proteome that can be targeted by small molecules. We recently described a strategy that integrates fragment-based ligand discovery with chemical proteomics to furnish global portraits of reversible small-molecule/protein interactions in human cells. Excavating clear structure-activity relationships from these 'ligandability' maps, however, was confounded by the distinct physicochemical properties and corresponding overall protein-binding potential of individual fragments. Here, we describe a compelling solution to this problem by introducing a next-generation set of fully functionalized fragments differing only in absolute stereochemistry. Using these enantiomeric probe pairs, or

SUBMITTER: Wang Y 

PROVIDER: S-EPMC6874898 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature