μMap Photoproximity Labeling Enables Small Molecule Binding Site Mapping.

ABSTRACT: The characterization of ligand binding modes is a crucial step in the drug discovery process and is especially important in campaigns arising from phenotypic screening, where the protein target and binding mode are unknown at the outset. Elucidation of target binding regions is typically achieved by X-ray crystallography or photoaffinity labeling (PAL) approaches; yet, these methods present significant challenges. X-ray crystallography is a mainstay technique that has revolutionized drug discovery, but in many cases structural characterization is challenging or impossible. PAL has also enabled binding site mapping with peptide- and amino-acid-level resolution; however, the stoichiometric activation mode can lead to poor signal and coverage of the resident binding pocket. Additionally, each

SUBMITTER: Huth SW 

PROVIDER: S-EPMC10809032 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature