Site‐Selective Itaconation of Complex Peptides by Photoredox Catalysis

Site‐selective peptide functionalization provides a straightforward and cost‐effective access to diversify peptides for biological studies. Among many existing non‐invasive peptide conjugations methodologies, photoredox catalysis has emerged as one of the powerful approaches for site‐specific manipulation on native peptides. Herein, we report a highly N‐termini‐specific method to rapidly access itaconated peptides and their derivatives through a combination of transamination and photoredox conditions. This strategy exploits the facile reactivity of peptidyl‐dihydropyridine in the complex peptide settings, complementing existing approaches for bioconjugations with excellent selectivity under mild conditions. Distinct from conventional methods, this method utilizes the highly reactive carbamoyl radical derived from a peptidyl‐dihydropyridine. In addition, this itaconated peptide can be further functionalized as a Michael acceptor to access the corresponding peptide‐protein conjugate. Photoredox catalysis has emerged as a powerful approach for site‐selective peptide functionalization. Herein, we report a highly N‐termini‐specific method to rapidly access itaconated peptide derivatives under mild photoredox conditions. Distinct from conventional methods that rely on residue nucleophilicity, this method proceeds through a highly reactive carbamoyl radical intermediate to achieve excellent selectivity. Itaconated peptides can be further functionalized to access peptide‐protein conjugates.