Photochemically-enabled, post-translational production of C-terminal amides.

ABSTRACT: C-terminal α-amidated peptides are attractive therapeutic targets, but preparative methods to access amidated pharmaceuticals are limited both on lab and manufacturing-scale. Here we report a straightforward and scalable approach to the C-terminal α-amidation of peptides and proteins from cysteine-extended polypeptide precursors. This amidation protocol consists of three highly efficient steps: 1) selective cysteine thiol substitution with a photolabel, 2) photoinduced decarboxylative elimination and 3) enamide cleavage by simple acidolysis or inverse electron demand Diels-Alder reaction. We provide a blueprint for applying this protocol to the semi-recombinant production of therapeutically relevant targets where gram scale C-terminal α-amidation is achieved in a photoflow reactor on a rec

SUBMITTER: Hymel D 

PROVIDER: S-EPMC11608224 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature