Chemoselective, regioselective, and positionally selective fluorogenic stapling of unprotected peptides for cellular uptake and direct cell imaging.

ABSTRACT: Peptide stapling reactions represent powerful methods for structuring native α-helices to improve their bioactivity in targeting protein-protein interactions (PPIs). In light of a growing need for regio- and positionally selective stapling methods involving natural amino acid residues in their unprotected states, we report a rapid, mild, and highly chemoselective three-component stapling reation using a class of molecular linchpins based on 2-arylketobenzaldehydes (ArKBCHOs) that create a fluorescent staple, hereafter referred to as a Fluorescent Isoindole Crosslink (FlICk). This methodology offers positional selectivity favouring i, i + 4 helical staples comprising a lysine and cysteine, in the presence of competing nucleophiles on unprotected peptides. In our efforts to fur

SUBMITTER: Dayanara NL 

PROVIDER: S-EPMC11605703 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature