Semax and Selank are two synthetic heptapeptides developed in Russia by attaching the same Pro-Gly-Pro tail to different natural fragments: Semax derives from adrenocorticotropic hormone ACTH(4-7), Selank from the immunopeptide tuftsin. Both are studied as nootropic and anxiolytic research peptides, with published work describing neurotrophin regulation for Semax and GABAergic and enkephalin-related effects for Selank. This guide covers derivation, structure, mechanism, specification and laboratory handling; research use only.
Key takeaways
- Semax is Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP), CAS 80714-61-0, C37H51N9O10S, MW 813.9 — the ACTH(4-7) fragment with a Pro-Gly-Pro extension.
- Selank is Thr-Lys-Pro-Arg-Pro-Gly-Pro (TKPRPGP), CAS 129954-34-3, C33H57N11O9, MW 751.9 — the tuftsin tetrapeptide with the same Pro-Gly-Pro extension.
- Tuftsin (Thr-Lys-Pro-Arg) was described by Najjar and Nishioka in Nature in 1970 as a phagocytosis-stimulating peptide released from immunoglobulin.
- The shared Pro-Gly-Pro tail is described in the literature as a stabilising motif that slows enzymatic breakdown of the parent fragment.
- For Semax, Dolotov and colleagues reported specific binding and raised brain-derived neurotrophic factor protein in rat basal forebrain in 2006 — the BDNF/TrkB axis is the most-cited mechanistic thread.
- For Selank, Zozulya and colleagues reported inhibition of enkephalin-degrading enzymes in 2001, and Volkova and colleagues reported altered expression of GABAergic genes in 2016.
- Both are small, water-soluble peptides with no cysteine residues; Semax carries a methionine that is oxidation-sensitive, which matters for storage.
- N-acetyl Semax amidate is a modified analogue with the N-terminus acetylated and the C-terminus amidated, both described as strategies for slowing exopeptidase attack.
What are Semax and Selank?
Semax and Selank are synthetic seven-residue peptides created at the Institute of Molecular Genetics in Moscow using the same design logic: take a short natural peptide fragment with known activity, then bolt a Pro-Gly-Pro tripeptide onto its C-terminus so that the resulting molecule survives longer in biological fluids. Semax started from a fragment of adrenocorticotropic hormone; Selank started from tuftsin.
That common design is why the two compounds are so often discussed together, and why they are supplied as a blend as well as individually. They are not chemically related beyond the shared tail — their parent fragments come from entirely different biology, one endocrine and one immunological — but they share a synthetic strategy, a size class and a research field.
In the research literature both are described as neuropeptide-derived compounds studied in cognition, stress and neuroprotection models, largely in rodent work and largely from Russian research groups. Non-Russian replication is comparatively thin, which is an honest limitation to state up front when planning experiments around either compound.
Derivation: ACTH(4-7) and tuftsin
Semax comes from adrenocorticotropic hormone, a 39-residue pituitary peptide. Residues 4 to 10 of ACTH had long been studied for behavioural effects that appeared separable from the hormone’s steroidogenic role, and Semax retains only residues 4 to 7 — Met-Glu-His-Phe — before the Pro-Gly-Pro extension. It is therefore usually described as an ACTH(4-7) or ACTH(4-10) analogue depending on which convention a paper follows.
Selank comes from tuftsin. Najjar and Nishioka reported tuftsin in Nature in 1970 as the phagocytosis-stimulating tetrapeptide Thr-Lys-Pro-Arg released enzymatically from the heavy chain of immunoglobulin G, naming it after Tufts University where the work was done. Selank is that tetrapeptide with Pro-Gly-Pro appended.
The Pro-Gly-Pro motif is not decorative. Proline residues resist cleavage by many common peptidases because of the constrained ring nitrogen, and the literature describes the tail as extending the effective lifetime of the parent fragment in plasma and tissue. Notably, Pro-Gly-Pro is itself a naturally occurring peptide fragment, which is part of the rationale given for choosing it.
Sequences and specification
Both peptides are short, linear, unmodified in their base forms, and free of cysteine — so there are no disulfide bridges to worry about and no risk of disulfide scrambling in solution. The relevant chemical vulnerabilities are the methionine in Semax, which oxidises, and the general susceptibility of any peptide backbone to hydrolysis in warm aqueous conditions.
Semax sequence, with the shared Pro-Gly-Pro tail marked:
MEHFPGP
Selank sequence, same convention:
TKPRPGP
| Product | Sequence | CAS | Formula | MW | Parent fragment |
|---|---|---|---|---|---|
| Semax | Met-Glu-His-Phe-Pro-Gly-Pro | 80714-61-0 | C37H51N9O10S | 813.9 | ACTH(4-7) |
| Selank | Thr-Lys-Pro-Arg-Pro-Gly-Pro | 129954-34-3 | C33H57N11O9 | 751.9 | Tuftsin |
| N-acetyl Semax amidate | Ac-Met-Glu-His-Phe-Pro-Gly-Pro-NH2 | Not assigned in public registries | Semax backbone, terminally modified | Higher than 813.9 | ACTH(4-7) |
| Semax + Selank blend | Both heptapeptides in one vial | n/a (mixture) | n/a | n/a | Both |
Semax: reported research pathways
The dominant mechanistic thread in the Semax literature is neurotrophin regulation. Dolotov and colleagues reported in the Journal of Neurochemistry in 2006 that radiolabelled Semax bound specifically in rat brain tissue and that treatment raised brain-derived neurotrophic factor protein in the basal forebrain, connecting the peptide to the BDNF/TrkB signalling axis.
Subsequent Russian work extended this to gene-expression profiling, describing changes in neurotrophin and neurotrophin-receptor transcripts across hippocampus, frontal cortex and retina after Semax administration in rodents. Transcriptome studies in cerebral ischaemia models have also been published, describing broad changes in inflammatory and vascular gene sets.
A second thread concerns peptidase inhibition. Semax, like Selank, has been reported to slow the enzymatic breakdown of enkephalins in human serum, which would prolong endogenous opioid peptide signalling — a mechanism proposed to contribute to the behavioural observations in animal work.
Selank: reported research pathways
Selank’s most-cited mechanism is inhibition of enkephalin-degrading enzymes. Zozulya and colleagues reported in Bulletin of Experimental Biology and Medicine in 2001 that Selank concentration-dependently inhibited enkephalin hydrolysis in human plasma, and proposed this as a route to its anxiolytic profile in animal models.
The second thread is GABAergic. Volkova and colleagues reported in Frontiers in Pharmacology in 2016 that Selank altered expression of genes involved in GABAergic neurotransmission in rat brain, and that the pattern of change correlated positively with that produced by GABA itself — evidence they interpreted as allosteric modulation of the GABA-A system rather than direct receptor agonism.
A third thread reflects Selank’s tuftsin ancestry: immune gene expression. Kolomin and colleagues reported altered expression of inflammation-related genes in mouse spleen in Regulatory Peptides in 2011 and characterised the time course of those changes in Molecular Immunology in 2014. This immunomodulatory dimension distinguishes Selank from most compounds studied as anxiolytics.
Modified analogues and the blend
Two variations on the base peptides appear in research catalogues. The first is terminal modification, most commonly N-acetyl Semax amidate, in which an acetyl group caps the free amino terminus and an amide group caps the carboxyl terminus. Both modifications are standard peptide-chemistry strategies for blocking exopeptidase attack, because aminopeptidases require a free N-terminal amine and carboxypeptidases require a free C-terminal acid.
The second is co-formulation. A Semax and Selank blend places both heptapeptides in a single lyophilised vial. From a laboratory standpoint a blend is convenient but analytically more demanding: the certificate of analysis should resolve and report both components separately, and chromatographic overlap between two peptides of similar size is a real possibility that a competent method development step must address.
Why terminal capping is used
Aminopeptidases attack a free N-terminal amine; carboxypeptidases attack a free C-terminal acid. Acetylation and amidation remove both handles, which is why acetylated, amidated analogues are described as more resistant to enzymatic trimming than their parent peptides.
What a blend certificate must show
Two resolved peaks with assigned identities, the ratio between them, and a mass spectrometry confirmation for each component. A single combined purity figure with no component breakdown does not demonstrate that the vial contains what the label claims.
Handling, stability and storage
Both peptides are supplied lyophilised and are freely water-soluble. The chief chemical liability specific to Semax is its N-terminal methionine, which oxidises to methionine sulfoxide on exposure to air, light and oxidising buffer components — a change of plus sixteen mass units that shows clearly on mass spectrometry and usually as a shoulder or early-eluting peak on reversed-phase chromatography.
Selank has no methionine and no cysteine, so its degradation profile is dominated by ordinary backbone hydrolysis rather than a specific residue vulnerability. Its arginine and lysine residues make it strongly basic, which is worth noting when selecting a buffer or an ion-pairing chromatographic method.
| Form | Condition | Typical working window | Notes |
|---|---|---|---|
| Lyophilised, sealed | −20 °C, dark, desiccated | Long term | Most stable state; keep the desiccant with the vial |
| Lyophilised, sealed | 2–8 °C, dark | Medium term | Acceptable while a batch is in active use |
| Lyophilised, sealed | Room temperature | Transit only | Short excursions are tolerated; return to cold storage on arrival |
| Reconstituted solution | 2–8 °C, dark | Short term | Semax: minimise headspace and light to limit methionine oxidation |
| Reconstituted, aliquoted | −20 °C or below, dark | Extended | Single-use aliquots; avoid repeated thawing |
Solution preparation concentration reference
The table below states the relationship between the mass of peptide in a vial and the volume of diluent added. It is a concentration reference for preparing laboratory solutions and carries no implication of administration to any organism. Full arithmetic is covered in our reconstitution guide.
- Equilibrate the vial. Bring it to room temperature while still sealed so that moisture does not condense on the lyophilised cake.
- Choose the diluent. Bacteriostatic water is the usual laboratory choice for multi-draw work; sterile water suits single-use preparations.
- Add slowly down the wall. Direct the stream against the glass rather than onto the cake to limit foaming.
- Swirl, do not shake. Rotate gently until fully dissolved; both peptides dissolve readily.
- Aliquot and protect from light. Amber tubes or foil, minimal headspace, immediate labelling.
- Record everything. Compound, batch, concentration, diluent, date — every aliquot, every time.
| Mass in vial | Diluent volume | Concentration | Amount per 0.1 mL | Approximate molarity |
|---|---|---|---|---|
| 10 mg Semax | 2 mL | 5 mg/mL | 500 mcg | ≈ 6.1 mM (MW 813.9) |
| 10 mg Semax | 5 mL | 2 mg/mL | 200 mcg | ≈ 2.5 mM |
| 10 mg Selank | 2 mL | 5 mg/mL | 500 mcg | ≈ 6.6 mM (MW 751.9) |
| 10 mg Selank | 5 mL | 2 mg/mL | 200 mcg | ≈ 2.7 mM |
| 20 mg blend | 2 mL | 10 mg/mL total | 1 mg total | Component-dependent |
| 30 mg NA-Semax amidate | 3 mL | 10 mg/mL | 1 mg | Use the certificate mass |
Purity, identity and the certificate of analysis
For short peptides such as these, a credible certificate shows reversed-phase HPLC purity with the chromatogram attached, mass spectrometry identity matching the expected monoisotopic or average mass, appearance, and a batch number that matches the vial label. Anything undated, unbatched or presented as a generic specimen is not evidence about the material in front of you.
Two impurity signatures are worth learning to spot. For Semax, a peak at plus sixteen mass units indicates methionine sulfoxide, which is oxidation rather than a synthesis failure and often reflects handling history. For any short synthetic peptide, deletion sequences — species missing one residue — indicate incomplete coupling during solid-phase synthesis, and appear as closely eluting peaks with predictable mass differences.
GenoPept publishes a per-batch third-party certificate covering HPLC purity and mass spectrometry identity at the COA certificates page. Our peptide purity testing guide explains how to read those documents in detail.
Semax and Selank in the GenoPept store
Frequently asked questions
What is the difference between Semax and Selank?
They share a design but not an origin. Semax is the ACTH(4-7) fragment Met-Glu-His-Phe with a Pro-Gly-Pro tail, and its literature centres on BDNF and neurotrophin signalling. Selank is the immunopeptide tuftsin, Thr-Lys-Pro-Arg, with the same tail, and its literature centres on GABAergic modulation, enkephalin-degrading enzyme inhibition and immune gene expression.
What is the Semax peptide sequence?
Semax is Met-Glu-His-Phe-Pro-Gly-Pro, written MEHFPGP in single-letter code. The first four residues correspond to positions 4 to 7 of adrenocorticotropic hormone; the final three are the synthetic Pro-Gly-Pro extension. Its CAS number is 80714-61-0, formula C37H51N9O10S and molecular weight 813.9.
What is Selank derived from?
Selank is derived from tuftsin, the tetrapeptide Thr-Lys-Pro-Arg that Najjar and Nishioka described in Nature in 1970 as a phagocytosis-stimulating fragment released from immunoglobulin G. Selank adds Pro-Gly-Pro to tuftsin’s C-terminus, giving the heptapeptide TKPRPGP with CAS number 129954-34-3 and molecular weight 751.9.
Why do both peptides end in Pro-Gly-Pro?
Proline-rich sequences resist many peptidases because proline’s ring nitrogen constrains the backbone geometry those enzymes require. The literature describes the Pro-Gly-Pro extension as a stabilising motif that lengthens the effective lifetime of the parent fragment, and Pro-Gly-Pro occurs naturally as a peptide fragment in its own right.
What is N-acetyl Semax amidate?
It is Semax with two terminal modifications: an acetyl group on the amino terminus and an amide group on the carboxyl terminus. Both are standard peptide-chemistry strategies for blocking exopeptidase attack, since aminopeptidases need a free N-terminal amine and carboxypeptidases need a free C-terminal acid. Confirm its mass from the batch certificate.
Does Semax need to be refrigerated?
Sealed lyophilised Semax is most stable at −20 °C in the dark with desiccant, and 2–8 °C is acceptable while a batch is in active use. Once in solution it should be kept cold, dark and aliquoted, because the N-terminal methionine oxidises on exposure to air and light, adding sixteen mass units.
Are Semax and Selank controlled drugs in the UK?
Neither Semax nor Selank is listed as a controlled drug under the Misuse of Drugs Act 1971. Neither holds a UK marketing authorisation as a medicine, so both are supplied here as laboratory research chemicals and must not be offered or used for human consumption. This is general information, not legal advice.
How strong is the evidence base for these peptides?
The published literature is real but narrow. Most mechanistic and behavioural studies come from a small number of Russian research groups, are conducted in rodents, and have limited independent replication elsewhere. Researchers planning experiments should treat the mechanistic claims as hypotheses to be tested rather than as established pharmacology.
References
- Najjar VA, Nishioka K. ‘Tuftsin’: a natural phagocytosis stimulating peptide. Nature. 1970;228(5272):672–673. Nature
- Zozulya AA, Kost NV, Sokolov OY, et al. The inhibitory effect of Selank on enkephalin-degrading enzymes as a possible mechanism of its anxiolytic activity. Bulletin of Experimental Biology and Medicine. 2001;131(4):315–317. PubMed
- Dolotov OV, Karpenko EA, Seredenina TS, et al. Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. Journal of Neurochemistry. 2006;97(1):82–86. DOI
- Volkova A, Shadrina M, Kolomin T, et al. Selank administration affects the expression of some genes involved in GABAergic neurotransmission. Frontiers in Pharmacology. 2016;7:31. DOI
- Kolomin T, Shadrina M, Andreeva L, Slominsky P, Limborska S, Myasoedov N. Expression of inflammation-related genes in mouse spleen under tuftsin analog Selank. Regulatory Peptides. 2011;170(1–3):18–23. DOI
- Kolomin T, Morozova M, Volkova A, et al. The temporary dynamics of inflammation-related genes expression under tuftsin analog Selank action. Molecular Immunology. 2014;58(1):50–55. DOI
Research-grade Semax and Selank, batch-verified
GenoPept supplies Semax and Selank as lyophilised vials with a per-batch third-party certificate of analysis covering HPLC purity and mass spectrometry identity, dispatched from the UK, strictly for laboratory research.