Reading Peptide Nomenclature: Sequences, Salt Forms, and Modifications

A peptide specification often looks like this:

H-Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val-OH, acetate salt

Every element of that carries information, and being able to read it lets you verify that what a certificate of analysis describes is what you intended to order. This is a guide to the notation.

One-letter and three-letter codes

Amino acids have two standard abbreviations. Three-letter codes are more legible for short sequences; one-letter codes are compact for long ones.

Amino acid	3-letter	1-letter	Amino acid	3-letter	1-letter
Alanine	Ala	A	Leucine	Leu	L
Arginine	Arg	R	Lysine	Lys	K
Asparagine	Asn	N	Methionine	Met	M
Aspartate	Asp	D	Phenylalanine	Phe	F
Cysteine	Cys	C	Proline	Pro	P
Glutamate	Glu	E	Serine	Ser	S
Glutamine	Gln	Q	Threonine	Thr	T
Glycine	Gly	G	Tryptophan	Trp	W
Histidine	His	H	Tyrosine	Tyr	Y
Isoleucine	Ile	I	Valine	Val	V

Two are worth memorising because they’re the ones that cause confusion: K is lysine, not the K-sounding option, and W is tryptophan. Neither follows from the name.

Direction: sequences are written N to C

Peptide sequences are conventionally written left to right from the N-terminus (free amino group) to the C-terminus (free carboxyl group).

This is not arbitrary. It’s the direction in which peptides are synthesised biologically, and the direction the convention preserves. A sequence written backwards is a different molecule.

The H- prefix and -OH suffix denote a free N-terminus and free C-terminus respectively — the unmodified default. Their presence in a specification is explicit confirmation rather than new information.

Terminal modifications

The termini are the most commonly modified positions, and the modifications appear in the name.

C-terminal amidation — written as -NH2 in place of -OH. The terminal carboxyl is replaced by an amide. This removes the negative charge that a free C-terminus carries at neutral pH, and it is a common modification.

N-terminal acetylation — written as Ac- in place of H-. An acetyl group caps the free amino group, removing the positive charge.

Both modifications change the molecule’s mass, which is why a certificate of analysis reporting observed mass will differ depending on which form was synthesised. A theoretical mass that doesn’t match observed by 1 Da is often an amidation discrepancy.

Salt forms

This is the element most likely to be omitted from a product listing, and it has practical consequences.

Peptides are purified by reverse-phase HPLC using trifluoroacetic acid (TFA) in the mobile phase. Basic residues — lysine, arginine, histidine, and the free N-terminus — end up paired with trifluoroacetate counter-ions. Without a deliberate salt exchange step, the finished peptide is a TFA salt.

Acetate salt material has been exchanged, replacing trifluoroacetate with acetate.

Why it matters:

Residual TFA can interfere with cell-based assays. It has documented effects on cell proliferation and viability in some systems, and it can interfere with certain analytical methods.
Counter-ions contribute to vial mass. The counter-ion fraction is part of why net peptide content is lower than total mass.
TFA absorbs in the far UV, which can complicate some spectroscopic work.

If your work is sensitive to it, specify the salt form when ordering rather than assuming.

Common suffixes and qualifiers

Fragment notation — (1-34) or similar indicates residues 1 through 34 of a larger parent sequence. So a “(1-34)” fragment is the N-terminal 34 residues, not an unrelated molecule.

This matters in practice: CJC-1295 (no DAC) with ipamorelin and the DAC version are different molecules, and results are not interchangeable between them. Sequences and salt forms are stated on every GH research product page.

Species prefixes — h for human, r for rat, m for mouse. Sequences differ between species, sometimes by a single residue, and that difference can matter for cross-reactivity.

D-amino acids — written as D-Ala or lowercase in one-letter notation. The standard biological amino acids are L-form; D-substitutions are deliberate and change the molecule’s three-dimensional structure and its resistance to proteolysis.

Cyclic peptides — indicated by cyclo(...) or by explicit disulfide notation showing which cysteine residues are paired. Disulfide connectivity is part of the molecule’s identity, and mass spectrometry alone will not confirm that the pairing is correct.

Worked example

Consider:

Ac-His-D-Phe-Arg-Trp-NH2, acetate salt

Reading it:

Ac- — N-terminus is acetylated
His-D-Phe-Arg-Trp — four residues, N to C, with the phenylalanine in D-form
-NH2 — C-terminus is amidated
acetate salt — counter-ions are acetate, not TFA

Both termini are capped, one residue is a D-substitution, and the salt has been exchanged. Each of those is a deliberate choice that affects mass, charge and behaviour.

What to check against a certificate of analysis

When a certificate arrives, the sequence on it should match the sequence you ordered, including:

Residue order and identity
Terminal modifications (H-/Ac-, -OH/-NH2)
Salt form
Any D-substitutions or non-standard residues
Fragment numbering, where applicable

A mismatch in any of these means you have a different molecule from the one you intended, even if the certificate is otherwise entirely legitimate.

References

IUPAC-IUB Joint Commission on Biochemical Nomenclature. Nomenclature and symbolism for amino acids and peptides. European Journal of Biochemistry, 1984;138(1):9–37. doi:10.1111/j.1432-1033.1984.tb07877.x
Andrushchenko VV, Vogel HJ, Prenner EJ. Optimization of the hydrochloric acid concentration used for trifluoroacetate removal from synthetic peptides. Journal of Peptide Science, 2007;13(1):37–43. doi:10.1002/psc.793
Cornish VW, Mendel D, Schultz PG. Probing protein structure and function with an expanded genetic code. Angewandte Chemie International Edition, 1995;34(6):621–633. doi:10.1002/anie.199506211
Roux S, Zékri E, Rousseau B, Paci M, Mory C, Fournier-Zaluski MC. Structural and biological effects of trifluoroacetate counter-ion in peptide preparations. Journal of Peptide Science, 2008;14(3):354–359. doi:10.1002/psc.951

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