Semax: What the ACTH Fragment Kept, and the 16-Dalton Peak
Semax is usually described as an ACTH(4–10) analog. That is close enough for a catalogue line and slightly wrong in a way that matters analytically, because the residues it did not keep are the ones that would otherwise dominate how it is measured.
The sequence, precisely
Semax is Met-Glu-His-Phe-Pro-Gly-Pro. The first four residues — methionine, glutamate, histidine, phenylalanine — are positions 4 to 7 of adrenocorticotropic hormone. Positions 8, 9 and 10 of ACTH are arginine, tryptophan and glycine, and Semax does not have them. In their place sits Pro-Gly-Pro.
So the accurate description is an ACTH(4–7) fragment carrying a synthetic C-terminal extension. The compound comes from the ACTH(4–10) region, which is where the looser phrasing comes from, but three of those residues were replaced rather than retained.
Why the tail is there
Pro-Gly-Pro is a stabilising tail, not a binding element. Proline’s side chain bonds back to its own backbone nitrogen, which locks the local geometry and makes the bond difficult for most exopeptidases to process. A short peptide without that protection is degraded from its ends quickly; with it, the molecule survives long enough to be studied.
The same three residues are attached to a completely different parent in Selank, which is tuftsin plus Pro-Gly-Pro. Two unrelated sequences, one stabilisation strategy — the tail is the shared engineering, not a family resemblance. Selank and its Pro-Gly-Pro tail covers the other half of the pair.
Losing the tryptophan changes two things
Tryptophan is the strongest chromophore in the standard amino acid set, and dropping ACTH’s Trp-9 has consequences for measurement rather than for anything else.
The first is detection. At 280 nm only tryptophan, tyrosine and to a small degree phenylalanine absorb. Semax retains one phenylalanine and nothing else aromatic, so its response at that wavelength is weak — and any impurity lacking aromatics is weaker still. Purity for this compound belongs at 214 nm or 220 nm, where the peptide bond itself absorbs and everything peptidic is visible. A high purity figure quoted at 280 nm on this sequence is describing the wavelength, not the material.
The second is that tryptophan is itself one of the most oxidation-prone residues, so its absence removes a common degradation route. Semax has a different one.
The methionine, and the 16-dalton peak
Position one of Semax is methionine, whose thioether sulfur oxidises readily to the sulfoxide. That reaction adds exactly one oxygen atom, and one oxygen is 16 daltons.
This is the single most useful thing to look for on a Semax mass spectrum. A peak 16 Da above the expected mass is oxidised material — a different compound from the one on the label, formed by exposure to air, light or peroxide contamination in a solvent rather than by a synthesis fault. It can appear after manufacture, which means a certificate showing none does not guarantee none later.
Practically, that makes air exposure the variable worth controlling: minimise repeat vial entries, keep the powder dry and dark, and do not leave reconstituted material standing open. How peptides degrade and aliquoting reconstituted peptides cover the handling side.
Identity figures
The molecular formula is C37H51N9O10S — note the sulfur, which is the methionine — for a mass of roughly 813.9 g/mol, against CAS registry number 80714-61-0. Those are the values to match across listings, since the naming is inconsistent and registry numbers are not. The calculated mass is also the reference point for the oxidation check above: 813.9 is the compound, 829.9 is the sulfoxide.
Behaviour on a column
Semax carries a glutamate and a histidine against a small, largely polar backbone, and it elutes early on a reversed-phase column. The oxidised form is more polar than the parent and elutes earlier still, which is why oxidation often shows up as a front shoulder on the main peak rather than as a cleanly separated impurity. A shallow gradient resolves it; a steep one buries it. Reading an HPLC chromatogram covers what that looks like in practice, and what a third-party peptide test actually measures covers which figures decide whether a number is meaningful.
What a certificate should show
The detection wavelength. The measured mass against 813.9, with attention to anything sitting 16 Da higher. And net peptide content, which accounts for counter-ion and residual water and is the figure that tells you how much peptide is actually in the vial — see net peptide content. Every report we hold is published in full on the certificates of analysis page.
How it is written
The compound appears as Semax, as the sequence MEHFPGP, and occasionally as ACTH(4–7)-PGP, which is the most accurate of the three. Descriptions using ACTH(4–10) refer to the region it derives from rather than to its actual composition.
What we supply
Semax is stocked as a 10mg vial, lyophilised, with identity data published on the product page. It is supplied for laboratory research use only. We publish no dosing information, no protocols involving human or veterinary subjects, and no statements about what the compound does in a person, and we do not provide them on request.
