Semax vs Selank: ACTH(4-7) and Tuftsin Heptapeptides Compared for Research

Semax and Selank are both synthetic heptapeptides, both under 820 g/mol, and both built the same way: a four-residue bioactive parent fragment with the tripeptide Pro-Gly-Pro bolted onto its C-terminus. Beyond that shared architecture they have almost nothing in common. Semax carries the Met-Glu-His-Phe core of corticotropin; Selank carries the Thr-Lys-Pro-Arg core of tuftsin, an immunopeptide released from the Fc region of IgG. In a Semax vs Selank comparison the practical question is rarely which peptide is "better" — it is which core fragment your assay is interrogating, and which of the two will survive your handling conditions unchanged.

Both are supplied as lyophilized powder at ≥ 99% by HPLC with lot-matched certificates, and both exist in the catalogue as vials, as pre-mixed nasal sprays and as a co-lyophilized blend. Everything below describes laboratory reference materials for in-vitro and preclinical work.

Semax vs Selank at a glance

Semax is Met-Glu-His-Phe-Pro-Gly-Pro, C37H51N9O10S, 813.93 g/mol, CAS 80714-61-0. Selank is Thr-Lys-Pro-Arg-Pro-Gly-Pro, C33H57N11O9, 751.89 g/mol, CAS 129954-34-3. Both are seven residues with free termini, both are freely water-soluble, and both are stored lyophilized at −20 °C and reconstituted at 2–8 °C. The 62 g/mol difference between them is almost entirely the sulfur atom and the aromatic ring that Semax has and Selank does not.

The shared Pro-Gly-Pro tail, and why both molecules have one

The native fragments on their own are poor laboratory reagents. ACTH(4-7) and tuftsin are tetrapeptides with free N- and C-termini, which makes them substrates for the aminopeptidases and carboxypeptidases present in serum, plasma and most tissue preparations; measured half-lives for unprotected short peptides in those matrices are minutes. Appending Pro-Gly-Pro addresses that sterically rather than chemically. Proline's ring constrains the backbone and removes the amide hydrogen that most exopeptidases require, so a C-terminal proline-rich extension blocks digestion inward from that end while leaving the N-terminal pharmacophore intact.

Pro-Gly-Pro is also not an inert spacer. It is itself a described glyproline, generated in vivo by collagen breakdown, and it appears in the literature as a short peptide with its own reported activity. For experimental design that matters in one specific way: a Pro-Gly-Pro-extended heptapeptide can in principle be cleaved at the junction to liberate both the parent tetrapeptide and free Pro-Gly-Pro, so any degradation study on either molecule should look for three species, not two.

What the two cores actually are

Semax: the corticotropin fragment without the hormone

Met-Glu-His-Phe is residues 4 to 7 of adrenocorticotropic hormone. The naming convention in the older literature calls Semax an ACTH(4-10) analog because it derives from that region of the hormone, but the sequence is not residues 4 to 10 of ACTH — it is residues 4 to 7 with a synthetic Pro-Gly-Pro tail. The point of the design is that the melanocortin-recognition motif survives while the rest of the hormone, including everything responsible for steroidogenic signalling, does not. Semax is studied as a neurotrophic probe, not an endocrine one: its documented research areas are BDNF and NGF expression, TrkB signalling, attention and memory paradigms, and cerebral ischaemia and oxidative-stress models.

Selank: the immunopeptide fragment

Thr-Lys-Pro-Arg is tuftsin, a tetrapeptide excised from the heavy chain of immunoglobulin G and described since the 1970s as a phagocytosis-stimulating factor. That lineage is why Selank's reported research areas straddle two fields that rarely share a reagent: GABAergic transmission and anxiolytic-type behavioural models on one side, cytokine expression and immune and stress-related gene expression on the other. The enkephalin-degrading enzyme activity listed on its specification is a third and separate line — Selank is studied as an inhibitor of enkephalin breakdown, which is a mechanism of action no ACTH fragment shares.

Charge is the difference that shows up at the bench

Count the ionisable side chains. Semax has one glutamate and one histidine: at pH 7 the carboxylate is deprotonated, the imidazole is mostly neutral, and with a free C-terminus the molecule sits around net −2. Selank has a lysine and an arginine, both protonated well above pH 10, giving a net charge near +1 once the free C-terminal carboxylate is counted. The two heptapeptides therefore behave as opposites in every charge-sensitive step of a workflow.

Three consequences are worth planning for. Cationic peptides adsorb to borosilicate glass and to untreated polypropylene, so dilute Selank solutions lose measurable material to the container wall — the usual mitigation is low-binding labware and a carrier protein or a small amount of acid in the diluent. On reversed-phase HPLC with the standard trifluoroacetic-acid ion-pairing system the two elute differently and predictably, with the dibasic peptide retained longer than its charge alone would suggest because the ion pair increases hydrophobicity. And in ion-exchange or capillary-electrophoresis identity work they migrate in opposite directions, which makes a mixed Semax and Selank preparation easy to resolve by charge-based methods and comparatively hard to resolve by mass alone, since 813.93 and 751.89 are close enough that low-resolution instruments can produce confusing adduct patterns.

Stability: one methionine versus none

Semax contains the only sulfur atom in either molecule. Methionine is the residue most prone to oxidation in stored peptides, converting to the sulfoxide with a 16 Da mass increase on exposure to air, light, trace metals and time, and the sulfoxide co-elutes close enough to the parent that a shallow gradient is needed to see it as a separate peak. Semax also carries a phenylalanine and a histidine; imidazole is a metal-coordinating group, which is the reason Semax should never share a vial with a copper peptide.

Selank has no methionine, no cysteine, no tryptophan and no asparagine. That removes oxidation, disulfide scrambling, photodegradation at the indole and asparagine deamidation — four of the five routes that normally shorten a peptide's shelf life. Its specification asks only that repeated freeze–thaw cycles be avoided, which is a mechanical and aggregation concern rather than a chemical one. In a side-by-side study the honest expectation is that Selank stock holds its assay value longer than Semax stock under identical conditions, and that a slow potency drift in a long Semax experiment is as likely to be chemistry as biology.

A proline artefact that is not an impurity

Both sequences contain three prolines, and the Xaa-Pro amide bond interconverts slowly between cis and trans conformers on the timescale of a chromatographic run. The visible result is a broadened or shouldered main peak, sometimes a resolved doublet, on an analytical gradient run at ambient temperature. It is conformational, not chemical, and it collapses into a single sharp peak when the column is run warm. Reading that shoulder as a 2–3% impurity and rejecting the lot is a recurring misinterpretation with proline-rich peptides; raising the column temperature is the check that settles it.

Choosing a format, and what the delivery route changes

Both peptides sit below the roughly 1,000 Da ceiling above which nasal absorption falls steeply in published models, which is why both are available as ready-made sprays and why the nootropic sequences dominate the nasal peptide spray range rather than the larger molecules in the catalogue. The format decision is about what you want to control.

The lyophilized vials — Semax in 5, 10 and 30 mg and Selank in 5 and 10 mg — are the only format in which concentration is a variable you set. Everything else ships at a fixed loading. The Semax nasal spray and the Selank nasal spray are each filled at roughly 0.67 mg/mL for the 10 mg bottle and 1.33 mg/mL for the 20 mg bottle, so a standard 0.1 mL metered actuation delivers approximately 67 or 133 micrograms respectively. The arithmetic and the pump-verification procedure are set out in the nasal spray formulation guide, and the gravimetric check matters here because a 67 microgram nominal actuation has no margin for a pump running 20% low.

Three combined formats exist. The co-lyophilized Semax + Selank vial fixes a 1:1 mass ratio in 10 mg or 20 mg total, which on a molar basis is close to 1:1.08 in Selank's favour because it is the lighter molecule — 5 mg of Semax is 6.14 micromoles against 6.65 micromoles for the same mass of Selank. The Semax + Selank nasal spray applies the same 1:1 mass split at approximately 0.33 or 0.67 mg/mL of each peptide, giving roughly 33 or 67 micrograms of each per actuation. The Selank + Semax dissolving strips put both peptides in a 20-strip fast-dissolving film at a fixed loading per strip, which is the format to reach for when the research question is specifically about the oral-transmucosal route rather than about either peptide.

Two further catalogue items contain Semax without Selank. The Focus dissolving strips combine Semax with NAD+ and methylene blue in a 30-strip pack — note that methylene blue is a redox-active phenothiazinium dye and stains everything it touches, so that pack is a three-component formulation study, not a Semax format. The Neuro Stack supplies Semax, Selank and Dihexa as three separately sealed vials with an individual certificate for each, which is the correct architecture for any design that needs to vary the three independently; the trade-offs between unmixed kits and co-formulated vials are covered in the peptide stacks guide.

Which to choose for which research question

Choose Semax for neurotrophic and melanocortin-fragment questions

If the endpoint is BDNF or NGF transcript or protein, TrkB phosphorylation, or performance in an attention or spatial-memory paradigm, Semax is the molecule with the matching literature. It is also the correct choice for ischaemia and oxidative-stress models, where most of the published work on this family sits, and for any structure–activity panel built around the ACTH(4-7) core — Adamax, an adamantane-modified analog described within the same Semax family, exists for exactly that kind of comparative panel.

Choose Selank for anxiolytic-type, GABAergic and immune endpoints

If the endpoint is GABA-receptor pharmacology, behaviour in an elevated-maze or open-field anxiety model, enkephalinase activity, or cytokine and stress-gene expression, Selank is the reagent. Its tuftsin parentage also makes it the appropriate probe when the question is whether an immunopeptide fragment retains immune activity after the Pro-Gly-Pro extension, which is a question Semax cannot address.

Run both when the variable is the tail, not the core

The pair is unusually well matched for one specific experiment: two peptides of near-identical length and identical C-terminal extension, with opposite net charge and entirely different parent fragments. That makes them a natural control pair for any study asking what the Pro-Gly-Pro tail contributes — to protease resistance, to mucosal permeation, or to measured recovery from a container — independently of the pharmacophore in front of it.

Purity, identity and COA checks

Ask for the same four things on both. Reversed-phase HPLC purity with the chromatogram attached, not just a number, so the proline shoulder is visible and interpretable. Mass-spectrometric identity against 813.93 for Semax and 751.89 for Selank, with the Semax spectrum inspected specifically for a +16 Da sulfoxide satellite. Sequence confirmation by MS/MS rather than by parent mass, because both molecules share the Pro-Gly-Pro tail and a mass-only check on a mixed or mislabelled lot is weak evidence. And water content, since a hygroscopic lyophilised cake that has taken up moisture reports a mass on the label that overstates the peptide actually present. How to read each of those sections is set out in the certificate-of-analysis guide.

Regulatory framing

Semax and Selank are supplied as research chemicals for in-vitro and preclinical laboratory work only. Neither is approved as a medicine in the United States or the European Union. Both have a regulatory history in the Russian Federation that does not transfer to research-grade material supplied anywhere else, and that history attaches to a specific pharmaceutical article rather than to a laboratory reagent. Nothing on this page describes human use, and no dosing or protocol guidance is given or implied.