What is Peptide sequence?
Also called: Primary structure, Amino acid sequence
The order of amino acids in a peptide chain, written by convention from the N-terminus (free amine) on the left to the C-terminus (free carboxyl) on the right.
By the APL Research Team · Updated
A peptide's sequence is the order of its amino acids, and almost everything else follows from it: mass, charge, solubility, chemical stability and biological activity. By convention it is written from N-terminus to C-terminus, left to right, the direction in which ribosomes build chains and the reverse of the direction used in solid-phase synthesis.
Reading the notation
| Notation | Example | Meaning |
|---|---|---|
| Three-letter, hyphenated | Thr-Lys-Pro-Arg-Pro-Gly-Pro | Selank, residue by residue |
| One-letter | TKPRPGP | The same peptide in compact form |
| N-terminal prefix | Ac-… | Acetylated N-terminus |
| C-terminal suffix | …-NH2 | C-terminal amide instead of a free acid |
| D- prefix, or lower-case letter | D-Phe, f | D-enantiomer of the residue |
| Named non-standard residue | Aib, 2-Nal | Residues outside the genetically encoded twenty |
| Bridge annotation | (Cys2–Cys7 disulfide) | A cross-link between two residues |
An unmodified sequence implies a free amine at the N-terminus and a free carboxylic acid at the C-terminus. Anything else should be written explicitly.
Worked example: Selank and Semax side by side
Selank (TKPRPGP) and Semax (MEHFPGP) are both seven residues long and end in the same three, Pro-Gly-Pro. Reading the rest of the sequence is enough to predict that they will behave differently at the bench:
| Selank | Semax | |
|---|---|---|
| Residues / peptide bonds | 7 / 6 | 7 / 6 |
| Basic groups | N-terminus, Lys, Arg | N-terminus, His |
| Acidic groups | C-terminus | Glu, C-terminus |
| Oxidation-prone residues | None | Met at position 1 |
| Trp or Tyr (strong 280 nm absorbance) | None | None |
| Average molecular weight | 751.87 g/mol | 813.92 g/mol |
Selank is strongly basic: as a salt it binds three counter-ions, and its isoelectric point is high. Semax is much closer to neutral and carries an N-terminal methionine that can oxidise to the sulfoxide, a +16 Da change detectable by mass spectrometry. Neither absorbs usefully at 280 nm, so neither can be quantified by the usual protein UV method.
Order matters even when composition does not
GHK and KHG contain the same three amino acids, share the formula C14H24N6O4 and both weigh 340.38 g/mol, yet they are different peptides. A single mass measurement cannot tell them apart; fragmentation (MS/MS) or chromatographic retention can. Terminal modifications matter just as much: BPC-157 as the free peptide is 1419.54 g/mol, while an N-acetylated, C-amidated version of the same fifteen residues would be 1460.59 g/mol, a difference any identity test would flag.
Common reading errors
- Reversing the direction, which describes a different molecule.
- Confusing similar one-letter codes: Q (Gln) with E (Glu), N (Asn) with D (Asp), K (Lys) with R (Arg).
- Dropping modifications when pasting a sequence into a calculator. The computed molecular weight changes, and so does every molar concentration derived from it.
The guide to reading peptide sequences covers notation in more depth, and the peptide molecular weight calculator accepts sequences with N-acetyl, C-amide and disulfide options.