Peptide nomenclature and modifications
How peptide sequences and modifications are written: one-letter and three-letter codes, the N-to-C convention, terminal groups such as Ac- and -NH2, cyclic and disulfide notation, D-residue prefixes, salt forms and the INCI names used for cosmetic peptides.
Why notation matters
A peptide's written sequence is a compact description of its chemical structure. Small notational details, such as whether the C-terminus is written as an acid or an amide, whether a residue is L or D, or whether two cysteines are bridged, correspond to real differences in mass, charge and behavior. A sequence that omits a modification describes a different molecule.
Consistent notation is also how a certificate of analysis, a compound page and a sequence tool are compared. If the sequence on a COA does not match the intended structure in every detail, the reported mass may be correct for the wrong molecule. This guide summarizes the conventions most often seen in research literature and product documentation, based broadly on IUPAC-IUBMB recommendations.
Codes and direction
Residues are written with three-letter codes separated by hyphens (Gly-His-Lys) or one-letter codes run together (GHK). Sequences are always written from the N-terminus on the left to the C-terminus on the right. The convention is so universal that it is rarely stated, which is why reversing a sequence by mistake produces a completely different peptide with the same composition and mass.
Three-letter codes are clearer for modified or non-standard residues, which are given their own abbreviations such as Aib, Nle, Orn or pGlu. One-letter codes are compact and used in databases, but non-standard residues need brackets or special symbols. A full list of codes is in the amino acid reference. Positions are numbered from the N-terminus, so a substitution may be written as, for example, [D-Trp6] to show the residue at position 6.
Terminal groups
A linear peptide has a free amine at the N-terminus and a free carboxylic acid at the C-terminus unless otherwise stated. Formal notation sometimes writes these explicitly as H- at the start and -OH at the end. Modifications replace these groups and are written as prefixes and suffixes.
Terminal groups change net charge and mass. Amidation turns a C-terminal acid into a neutral amide, a change of about 1 Da that is easy to miss in a mass spectrum but significant for receptor activity in many hormones. Acetylation adds 42 Da and removes the N-terminal positive charge.
- H-: free N-terminal amine (often omitted)
- Ac-: N-terminal acetylation, as in PT-141 and setmelanotide
- pGlu-: N-terminal pyroglutamate, sometimes also written Pyr- or Glp-
- Palm- or Pal-: N-terminal palmitoyl group, as in palmitoyl pentapeptide-4
- -OH: free C-terminal carboxylic acid
- -NH2: C-terminal amide, as in oxytocin and ipamorelin
- -NHEt or other alkyl amides: substituted C-terminal amides, as in some GnRH analogues
Cyclization and disulfide bonds
Cyclic peptides are written in several ways. Square or round brackets preceded by cyclo, such as cyclo[Asp-His-D-Phe-Arg-Trp-Lys], mark the residues that form a ring. When only part of a sequence is cyclic, the ring is bracketed within the linear sequence, as in Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 for melanotan II. Side-chain lactam bridges may also be noted with the linked residues, for example (Asp2–Lys7 lactam).
Disulfide bonds are usually written as a note after the sequence, such as (disulfide bridge: Cys1–Cys6) or with a line drawn between cysteines in a structure diagram. Peptides with more than one disulfide must state which cysteines pair, because different pairings give different isomers of identical mass. Forming a disulfide removes two hydrogen atoms, so the oxidized form is 2 Da lighter than the reduced form. See cyclic peptides and disulfide bonds.
Stereochemistry and side-chain modifications
Residues are assumed to be L unless marked. D-residues are written with a D- prefix, such as D-Phe or D-Trp, and in one-letter notation some authors use lower-case letters (f for D-Phe), although this convention is not universal and should be defined where used. Achiral residues such as glycine and Aib have no L or D form. More on stereochemistry is in D-amino acids and retro-inverso peptides.
Side-chain modifications are shown in parentheses after the residue. Examples include Lys(palmitoyl), Lys(Ac), Ser(PO3H2) for phosphoserine, Met(O) for methionine sulfoxide and Cys(Acm) for a protected cysteine. Lipidated drugs such as semaglutide are described with the full linker and fatty acid on a specified lysine. Copper or other metal complexes are written with the metal after a hyphen or in a separate formula, as in GHK-Cu.
Salt forms and hydrates
Because most synthetic peptides are isolated as salts, product names and COAs often include the counter-ion. Common forms are written as acetate salt, trifluoroacetate or TFA salt, and hydrochloride or HCl salt. Formal formulas may show a variable number of counter-ions and water molecules, for example as · x CH3COOH · y H2O, because the exact stoichiometry varies between lots.
The molecular weight printed beside a name may refer to the free peptide or to a specific salt, and the two can differ substantially for basic sequences. For concentration calculations, use the free-peptide molecular weight together with net peptide content. See counter-ions: TFA vs acetate and purity vs net peptide content.
INCI names, codes and synonyms
Cosmetic ingredients are listed under International Nomenclature of Cosmetic Ingredients (INCI) names, which describe a peptide by its modification, length and an assigned number rather than its sequence. The number distinguishes different sequences of the same length and carries no chemical meaning, so an INCI name alone does not reveal the sequence. INCI names are occasionally reassigned, as with acetyl hexapeptide-8, formerly listed as acetyl hexapeptide-3.
Drug peptides accumulate several names over development: a company code, an international nonproprietary name and one or more brand names. Research peptides may carry informal names that are not systematic at all. When names conflict, the sequence with all modifications is the definitive identifier.
- Acetyl hexapeptide-8: the INCI name for Argireline
- Palmitoyl pentapeptide-4: the INCI name for Matrixyl
- Acetyl octapeptide-3: the INCI name for Snap-8
- Copper tripeptide-1: the INCI name for the copper complex of GHK
Frequently asked questions
What does -NH2 at the end of a peptide sequence mean?
It indicates C-terminal amidation: the terminal carboxylic acid has been replaced by a carboxamide. This removes a negative charge, slightly lowers the mass compared with the free acid, and is important for the activity of many natural peptide hormones. A sequence written without -NH2 is normally assumed to end in a free acid.
How is a cyclic peptide written?
Head-to-tail and side-chain cyclic peptides are usually written with the ring residues inside brackets preceded by cyclo, for example cyclo[Asp-His-D-Phe-Arg-Trp-Lys]. Disulfide-bridged peptides are generally written as a linear sequence with a note identifying which cysteines are bonded. For multiple disulfides, the pairing must be specified.
Does an INCI name tell you a peptide's sequence?
No. An INCI name such as palmitoyl pentapeptide-4 states the modification and the number of residues, but the trailing number is an assigned identifier that distinguishes different sequences of the same length. The actual sequence has to be found in the ingredient's technical documentation or the scientific literature.
Compounds mentioned
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