--- title: "C-terminal amidation and N-terminal acetylation" description: "What terminal modifications are, how they change charge and mass, and how they are introduced in synthesis." canonical: https://www.sablepeptides.co.uk/ref/terminal-modifications publisher: Sable Peptides Limited (UK company 17488610) note: Research use only. Not for human or veterinary use. --- # 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)](/ref/solid-phase-peptide-synthesis) - [Monoisotopic vs average molecular mass](/ref/monoisotopic-vs-average-mass) - [Peptide solubility in lab terms](/ref/peptide-solubility-reconstitution) - [Reference index](/ref) ## Sources 1. Alsina J et al. Solid-phase synthesis of C-terminal modified peptides. *Biopolymers*. 2003. PMID: [14517898](https://pubmed.ncbi.nlm.nih.gov/14517898/) 2. 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](https://pubmed.ncbi.nlm.nih.gov/7764886/) 3. Logerot E et al. Revealing C-terminal peptide amidation by the use of the survival yield technique. *Anal Biochem*. 2022. PMID: [35921876](https://pubmed.ncbi.nlm.nih.gov/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](/coa-request) and we email it within 2 hours. Research use only. Not for human or veterinary use. ## Cite this Research use only. Not for consumption. No health claims. Plain Sable Peptides. (2026). terminal-modifications. UK Research Peptide Reference. Retrieved 11 October 2026, from https://www.sablepeptides.co.uk/ref/terminal-modifications APA Sable Peptides. (2026, October 11). \*terminal-modifications\*. UK Research Peptide Reference. https://www.sablepeptides.co.uk/ref/terminal-modifications BibTeX @misc{sable\_terminal-modifications\_2026, author = {{Sable Peptides}}, title = {{terminal-modifications}}, year = {2026}, howpublished = {\\url{https://www.sablepeptides.co.uk/ref/terminal-modifications}}, note = {Accessed 11 October 2026. CC BY 4.0} } Badge Data: UK Research Peptide Reference — Sable Peptides Date modified: 2026-10-16 Reviewed by Sable Peptides editorial team · 14 October 2026 · [Editorial policy](/editorial-policy)