C-terminal amidation and N-terminal acetylation
C-terminal amidation and N-terminal acetylation
Last updated: 2026-10-10 · Research use only. Not for human or veterinary use.
Short answer
Terminal modifications cap a peptide's ends. C-terminal amidation replaces the free carboxylic acid with a carboxamide (−0.984 Da) and removes a negative charge; N-terminal acetylation adds an acetyl group (+42.01 Da) and removes a positive charge. Many natural peptides are amidated, and synthetic versions reproduce this with amide-forming resins. [1]
At a glance
| Term | Definition / specification |
|---|---|
| C-terminal amide | –CONH2 instead of –COOH; −0.984 Da; loses −1 charge |
| N-terminal acetyl | CH3CO– on N-terminus; +42.011 Da; loses +1 charge |
| Synthesis route (amide) | Rink amide or similar resin in Fmoc SPPS |
| Synthesis route (acetyl) | Acetic anhydride capping after final deprotection |
| Effect | Changes charge, solubility and resistance to exopeptidases |
| Confirmation | MS mass difference vs free-acid/free-amine form |
Notation
Sequences often show amidation as –NH2 and acetylation as Ac– (for example Ac-…-NH2).
Why check
Amide and acid forms differ by under 1 Da, so high-resolution MS or HPLC retention is needed to confirm the right form.
FAQ
How do I know if a peptide is amidated?
The sequence notation ends in -NH2 and the observed mass is about 1 Da lower than the free acid.
Does amidation change solubility?
It can, because it removes the negative C-terminal charge.
Related reference pages
- Solid-phase peptide synthesis (SPPS)
- Monoisotopic vs average molecular mass
- Peptide solubility in lab terms
- Reference index
Sources
- Alsina J et al. Solid-phase synthesis of C-terminal modified peptides. Biopolymers. 2003. PMID: 14517898
- Merkler DJ C-terminal amidated peptides: production by the in vitro enzymatic amidation of glycine-extended peptides and the importance of the amide to bioactivity. Enzyme Microb Technol. 1994. PMID: 7764886
- Logerot E et al. Revealing C-terminal peptide amidation by the use of the survival yield technique. Anal Biochem. 2022. PMID: 35921876
---
Research use only. This page describes laboratory chemistry and analytical methods. It is not advice on any use in people or animals.
CoA for every lot — request yours and we email it within 2 hours.
Research use only. Not for human or veterinary use.