Amidation
A chemical modification in which the C-terminal carboxyl group of a peptide is converted to an amide group. Amidation is common in natural peptide hormones and often enhances receptor binding affinity and resistance to degradation by carboxypeptidases.
Technical Context
Approximately half of all bioactive peptide hormones in humans are C-terminally amidated. The amidation reaction is catalysed by the enzyme peptidylglycine alpha-amidating monooxygenase (PAM), which converts a C-terminal glycine-extended precursor to the amidated product. Amidation neutralises the negative charge of the C-terminal carboxyl group, which often improves receptor binding — many peptide receptors have evolved to recognise the amidated form. It also protects against carboxypeptidase degradation. In synthetic peptide manufacturing, C-terminal amidation is readily achievable using Rink amide resin during SPPS. Octreotide, goserelin, leuprolide, and many other approved peptides feature this modification.