Selank and Semax: Two Heptapeptides Built the Same Way

Selank and Semax are both seven-residue peptides, both came out of the same research tradition, and both are constructed on the same architectural idea: take a short biologically derived fragment and attach a three-residue tail to it. Understanding that shared design makes the pair much easier to keep straight, and it explains why each has a characteristic impurity profile that the other does not. It also explains the N-acetyl question, which is the single most common source of identity confusion in this group.

The identity data

The shared design: a fragment plus Pro-Gly-Pro

Read the two sequences from the right. Both end in Pro-Gly-Pro. That tripeptide is not incidental; it is the same structural addition in both molecules, appended to a different four-residue head.

Selank head is Thr-Lys-Pro-Arg, which is tuftsin, a naturally occurring tetrapeptide. Semax head is Met-Glu-His-Phe, which corresponds to the 4 to 7 region of adrenocorticotropic hormone. So Selank is tuftsin plus PGP, and Semax is ACTH(4-7) plus PGP. Once that is clear, the names stop being arbitrary syllables and the two stop being confusable.

The proline content that follows from this design has an analytical consequence worth knowing. Selank contains three prolines and Semax two, all clustered at or near the C-terminus. Proline-rich sequences are conformationally constrained, they can present as multiple slowly interconverting forms on a chromatographic timescale, and the result is peak shapes that are broader or occasionally doubled in a way that is a property of the molecule rather than a sign of impurity. A method developed on a proline-free peptide may produce a chromatogram for these two that looks worse than the material actually is.

The methionine in Semax, and what it does

Look at the formulas. Semax ends in S; Selank has no sulfur. That sulfur is the N-terminal methionine, and it is the single most consequential difference between the two from an analytical standpoint.

Methionine oxidizes readily, to the sulfoxide, and the resulting species is 16 units heavier than the parent. On a molecule of 813.9, a peak at roughly 830 is therefore the expected degradation product rather than a mystery contaminant, and it is the first thing to look for when a Semax chromatogram shows a shoulder or a near-neighbour peak. Oxidation proceeds on exposure to air and is faster in solution than in a sealed lyophilized powder, which is the practical reason the interval between reconstitution and use matters more for this compound than for a sulfur-free peptide of similar size.

Selank has no equivalent liability. Its arginine and lysine make it more strongly basic, which affects retention and salt form rather than stability.

N-acetyl: the 42-unit question

Both compounds are also supplied, by various sources, in N-acetylated form, in which an acetyl group is attached to the N-terminus. This is a real chemical modification and it adds 42 units to the mass. N-acetyl Semax is therefore near 856, and N-acetyl Selank near 794.

The trouble is that listings frequently drop the prefix. A page headed simply Semax may be describing the plain peptide or the acetylated one, and a certificate reporting a mass 42 units away from your reference value is far more likely to be documenting a different form than to be documenting a defective batch. There are also amidated variants in circulation, which shift the mass again. Before concluding that two documents disagree, establish which form each of them is for. The CAS numbers above are for the plain, unmodified peptides.

Counter-ions and what the milligram figure means

Both are basic peptides isolated as salts, typically acetate or trifluoroacetate, and the counter-ion adds mass without adding peptide. Where a certificate reports net peptide content, it is answering how much of the vial contents is peptide; purity is answering how much of that peptide is the target sequence. They are separate figures and comparing one against the other across two suppliers manufactures a discrepancy that is not there.

Documentation for this pair

Two seven-residue white powders in the same category is a fair argument for not identifying a vial by reading its label. Published batch documents are on the certificates of analysis page, and each is matched to a vial by cap colour and crimp colour. Coverage is partial, in that not every product and not every batch has a published certificate, and testing on published batches is by HPLC together with purity testing. The commitments, and the claims we specifically do not make, are on the purity guarantee page.

Both, in the Canadian catalogue

Selank 5mg, Selank 10mg and Semax 10mg are stocked in Canada under neuropeptides, alongside DSIP, which we have covered separately in DSIP: identity and analysis, and Kisspeptin-10. Current pricing is on the Canadian price index. Where both a 5 mg and a 10 mg presentation exist, they are the same compound and the difference is quantity per vial and therefore cost per milligram; one vial also means one batch and one certificate, which is worth weighing if consistency across a series of preparations matters to you.

The essentials

Selank is tuftsin plus Pro-Gly-Pro at 751.9. Semax is ACTH(4-7) plus Pro-Gly-Pro at 813.9. The sulfur in the Semax formula is a methionine, and a peak 16 units heavy is its expected oxidation product. Both circulate in N-acetylated form 42 units heavier than the plain peptide, and listings often omit the prefix, so verify the form before treating a mass difference as a defect. Proline-rich sequences produce chromatograms that can look messier than the material is.

All compounds referenced here are supplied by ExoLabz for laboratory research use only. They are not for human or veterinary use, are not authorised by Health Canada as a drug or natural health product, and nothing on this page is guidance on preparation, administration or use.