Acrolein-Mediated Conversion of Lysine to Electrophilic Heterocycles for Protein Diversification and Toxicity Profiling.

ABSTRACT: Understanding protein interactions in the presence of biological metabolites is critical for unraveling biological processes and advancing therapeutic interventions. This study focuses on α,β-unsaturated carbonyls, particularly acrolein-derived protein modifications, unveiling a one-pot, four-step, selective chemistry that results in the formation of a heterocyclic α,β-unsaturated carbonyl, termed 3-formyl-3,4-dehydropiperidino (FDP), exclusively on lysine residues. Remarkably, this chemistry transforms lysine, a nucleophile, into an electrophilic warhead. We demonstrate its versatility in late-stage peptide diversification, precision protein engineering, and homogeneous protein labeling with diverse payloads. Additionally, FDP-lysine smoothly transforms into another heterocycle, 3-methylp

SUBMITTER: Paikin ZE 

PROVIDER: S-EPMC11848821 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature