Amide (C-Terminal Amidation)

In C-terminal amidation, the carboxylic acid that ends a peptide chain becomes a primary amide — shown as –CONH2, or as a closing "-NH2" on a sequence line. The change takes away one negative charge and makes the molecule roughly 0.98 Da lighter than the free-acid version. It reproduces a real post-translational modification: in living cells, the enzyme peptidylglycine alpha-amidating monooxygenase generates it from a C-terminal glycine.

Typical amidated peptides

A large share of native signalling peptides carry the amide and lose most of their receptor activity if it is missing; examples include oxytocin, gastrin, calcitonin, PACAP and the growth hormone-releasing peptides. Research analogs copy this: Ipamorelin, GHRP-2 and GHRP-6 come as C-terminal amides, and compounds like N-Acetyl Semax Amidate combine the amide with an acetylated N-terminus. Product names normally make it obvious with the words "amide" or "amidate".

Practical consequences

There are two. First, the amide stops carboxypeptidases from clipping the chain, so amidated analogs tend to have longer in vitro half-lives than the corresponding free acids. Second, it moves the target value for identity testing: a mass spectrometry reading has to be checked against the theoretical molecular weight of the amidated molecule, otherwise the lot appears 1 Da too light. When a vendor’s sequence line and its MS value contradict each other on amidation, regard identity on the certificate of analysis as not confirmed.

Related terms

peptide bond · Ipamorelin.