Target Agnostic Photoaffinity Labelling by Sulfonylhydrazones.

ABSTRACT: Photoaffinity labeling is a widely used methodology for interrogating small molecule-protein interactions. However, these applications are limited by the few photo-crosslinkers that typically modify the affinity and the binding mode of the original ligand. Here, we report the development of new target agnostic photoaffinity warheads, sulfohydrazones that form a reactive carbene upon UV irradiation. Careful optimization of the reaction conditions allowed us to effectively label five different amino acid residues in proteins. Our approach turned biologically relevant hydrazones and sulfohydrazones to intrinsically irreversible covalent binders without structural modifications by photoactivation as demonstrated on monoamine oxidase A (MAO-A) enzyme and STAT5b (Signal transducer and activator

SUBMITTER: Garami K 

PROVIDER: S-EPMC12015381 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature