Definition
C-terminal amidation converts the terminal carboxylic acid (–COOH) into a carboxamide (–CONH2). In nature, the enzyme peptidylglycine alpha-amidating monooxygenase produces it from a glycine-extended precursor, and roughly half of known neuropeptides and peptide hormones are amidated, including oxytocin, vasopressin, calcitonin, amylin and GHRH. Amidation removes a negative charge, which can strengthen receptor interaction and slow carboxypeptidase degradation. In solid-phase synthesis, amidated peptides are made on Rink amide or similar resins that release the amide on cleavage. The change lowers mass by about 1 Da relative to the free acid, a small difference that mass spectrometry should resolve and a certificate of analysis should state.