Site-Selective Protein Modification via Peptide-Directed Proximity Catalysis.

ABSTRACT: Proximity catalysis exploits ligand binding for localized, catalytic protein modification. In this work, we introduce catalyst-functionalized peptides as versatile ligands for this approach. Through the functionalization of target-binding peptides with pyridinium oxime catalysts, we show that model proteins can be site-selectively modified with a variety of N-acyl-N-alkylsulfonamide reagents to introduce common functionalities, including fluorophores and affinity handles to the protein surface. Critically, we show that simple changes to the peptide-catalyst structure, moving the pyridinium oxime from the N- to C-terminus, alter the site of modification. This opens up possibilities to develop peptide libraries for a particular target protein and subsequently tuning the modific

SUBMITTER: Raynal L 

PROVIDER: S-EPMC12756790 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature