The Enzymology of Peptide Amidation

Since the 1950’s, it has been recognized that most peptide hormones contain a C-terminal amide3–6. In the last 40 years, over 100 amidated peptides have been identified7,8 and structure-activity relationships have shown that the C-terminal amide is key to the activity elicited by most amidated peptides9–12. The amide moiety arises by the post-translational, oxidative cleavage of a C-terminal glycine-extended prohormone (peptidyl-Gly) at the a-carbon of the glycine in a reaction which requires a reducing equivalent, copper, and O2 13,14. Peptidylglycine α-amidating enzyme (α-AE, EC 1.14.17.3)15,16 is the enzyme that catalyzes this reaction in vivo. In this review, we will focus on the chemical and enzymological aspects of peptide amidation. For more comprehensive treatments of the subject, two recent reviews are recommended8,17.