Reading a peptide sequence is simple once you know two conventions: the amino acid one-letter and three-letter codes, and the rule that sequences are written from the N-terminus on the left to the C-terminus on the right. This guide covers both, plus the shorthand used for modifications, so a sequence on a product page or certificate of analysis reads as clearly as a sentence.
Quick answer
How do you read a peptide sequence? Read it left to right, from the N-terminus to the C-terminus, using the standard amino acid codes defined by IUPAC-IUB. “GHK” means glycine, histidine, lysine. Prefixes such as “Ac-” and suffixes such as “-NH2” mark chemical modifications at the ends of the chain.
Direction: N-terminus to C-terminus
Every linear peptide has two chemically different ends. One carries a free amino group (the N-terminus) and the other a free carboxyl group (the C-terminus). By convention the N-terminal residue is written first. Reversing a sequence therefore does not describe the same molecule: GHK and KHG contain the same three amino acids but are different compounds with different properties. For the chemistry behind the backbone, see what a peptide is.
The 20 standard amino acid codes
These codes come from the IUPAC-IUB Joint Commission on Biochemical Nomenclature recommendations listed in the sources.
| Amino acid | 3-letter | 1-letter |
|---|---|---|
| Alanine | Ala | A |
| Arginine | Arg | R |
| Asparagine | Asn | N |
| Aspartic acid | Asp | D |
| Cysteine | Cys | C |
| Glutamine | Gln | Q |
| Glutamic acid | Glu | E |
| Glycine | Gly | G |
| Histidine | His | H |
| Isoleucine | Ile | I |
| Leucine | Leu | L |
| Lysine | Lys | K |
| Methionine | Met | M |
| Phenylalanine | Phe | F |
| Proline | Pro | P |
| Serine | Ser | S |
| Threonine | Thr | T |
| Tryptophan | Trp | W |
| Tyrosine | Tyr | Y |
| Valine | Val | V |
The same recommendations define ambiguity codes: B for “aspartic acid or asparagine”, Z for “glutamic acid or glutamine”, and X for an unknown or unspecified residue. You will rarely see them in a synthetic research sequence, where every position should be defined.
Why some letters do not match the name
Several amino acids share first letters, so the one-letter system could not give everyone their initial. Alanine, arginine, asparagine and aspartic acid all begin with A, for example, and only alanine gets it. The others received less obvious letters: R for arginine, N for asparagine, D for aspartic acid, and likewise K for lysine, F for phenylalanine, W for tryptophan, Y for tyrosine, Q for glutamine and E for glutamic acid. The three-letter codes are easier to decode by eye, which is why many certificates use them.
Notation for modifications and special residues
Synthetic peptides often carry chemical changes at the ends or in the chain. The common shorthand:
- Ac- at the start: the N-terminus is acetylated, removing its positive charge.
- -NH2 at the end: the C-terminus is an amide rather than a free acid. -OH marks the free acid explicitly.
- D- before a residue, for example D-Phe: that position uses the D-enantiomer instead of the natural L-form.
- cyclo(...) or a note on a disulfide bond: the chain is closed into a ring, either head to tail or through side chains.
- Non-standard residues such as norleucine (Nle) or aminoisobutyric acid (Aib) are written with their own abbreviations.
Cyclic and modified sequences are common in receptor research; the melanocortin analogs discussed in MT-2 and melanocortin research are examples.
Two worked examples
GHK reads glycine–histidine–lysine, a tripeptide with glycine at the N-terminus. Ala-Glu-Asp-Gly, written AEDG in one-letter code, is the tetrapeptide known as epitalon, discussed in the epitalon research overview.
Once the sequence is clear, it connects directly to documentation. The expected monoisotopic or average mass on a certificate is calculated from the sequence and any modifications. A mass spectrometry result that matches that expected mass supports identity, which is the subject of HPLC vs mass spectrometry.
Key takeaways
- Sequences run left to right, from the N-terminus to the C-terminus.
- IUPAC-IUB defines the one-letter and three-letter amino acid codes.
- Some one-letter codes are not initials, because several amino acids share first letters.
- Ac-, -NH2, D- and cyclo() describe modifications that change the molecule and its expected mass.
- The written sequence is what identity testing is checked against.
Frequently asked questions
Which end of a peptide sequence is written first?
The N-terminus, the end with the free amino group. The C-terminus, with the free carboxyl group or its modification, is written last.
Why is lysine abbreviated K?
L was already assigned to leucine, so lysine received a different letter. The same constraint explains R for arginine, F for phenylalanine and W for tryptophan.
What does -NH2 at the end of a sequence mean?
It means the C-terminus is amidated rather than a free carboxylic acid. The change removes a negative charge and alters the expected molecular mass by about one dalton.
What does X mean in a sequence?
X marks an unknown or unspecified amino acid. A defined synthetic research sequence should not contain one.
Sources
- IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature and symbolism for amino acids and peptides. Recommendations 1983. Eur J Biochem. 1984;138(1):9-37. doi:10.1111/j.1432-1033.1984.tb07877.x
For laboratory and in-vitro research use only. Not for human or veterinary use.
For laboratory and in-vitro research use only. Not for human or veterinary use. See our research-use disclaimer.
