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

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.

Using PAT to accelerate the transition to continuous API manufacturing.

Significant improvements can be realized by converting conventional batch processes into continuous ones. The main drivers include reduction of cost and waste, increased safety, and simpler scale-up and tech transfer activities. Re-designing the process layout offers the opportunity to incorporate a set of process analytical technologies (PAT) embraced in the Quality-by-Design (QbD) framework.