N-Acetyl Semax (Ac-Semax)

N-Acetyl Semax is Semax carrying an acetyl group on the free alpha-amino nitrogen of its N-terminal methionine, a single change that removes the terminal positive charge, caps the residue aminopeptidases attack first, and alters how the chain coordinates copper(II). The sequence is untouched: Met-Glu-His-Phe-Pro-Gly-Pro becomes Ac-Met-Glu-His-Phe-Pro-Gly-Pro. The acetylated free acid has the formula C39H53N9O11S and a molecular weight near 856.0 g/mol, against C37H51N9O10S and 813.9 g/mol for Semax. The Pro-Gly-Pro tail already protects the parent’s C-terminus, so this variant is capped at both ends.

Two acetylated variants circulate under near-identical names. The one described here keeps a free carboxyl C-terminus. The other, N-acetyl semax amidate, is acetylated and also amidated, giving C39H54N10O10S, 855.0 g/mol and CAS 2920938-90-3. PubChem holds a single record for both, CID 172638603, so a lookup on the plain name returns the amidated structure. The product listed on this site is described as an N-acetylated analogue with no amide specified, so this page describes the acetylated form, supplied as lyophilized (freeze-dried) reference powder for laboratory research use only.

The acetylated analogue came from the same Russian programme as the parent. Semax was developed at the Institute of Molecular Genetics in Moscow, its Pro-Gly-Pro tail added to slow cleavage from the C-terminal end. That left the N-terminal methionine exposed, and an acetyl cap answers it directly.

Shevchenko and colleagues reported the proteolytic behaviour of acetylated Semax in biological media in 2013 (PubMed 23652441), and Magri and colleagues characterised the modification chemically in 2016, comparing copper(II) and zinc(II) coordination by Semax and Ac-Semax in an SH-SY5Y neuroblastoma line (PubMed 27586814). For the parent, Dergunova and colleagues examined transcript changes after reversible cerebral ischemia in rats (PubMed 34097675), and Kolbaev and colleagues reported intracellular calcium dynamics in rat brain neurons (PubMed 41171324).

The evidence base for the acetylated form is very small, and that is the most useful thing to know about it. Indexed literature naming it runs to two chemistry and stability papers alone. Almost every published Semax result was generated with the unmodified parent, and no study has compared the two in an animal model.

The literature specific to N-Acetyl Semax concerns what the acetyl cap does to the molecule rather than what the molecule does to a cell. The free N-terminal amine is a coordinating donor atom, and removing it changes metal binding. Semax binds copper(II) through a CuN4 chromophore, while the acetylated peptide forms a distorted CuN3O species with a weak apical contribution from the methionine sulphur and carries the more positive formal redox potential (PubMed 27586814).

The distinction needed here is three-way: parent, acetylated analogue, amidated analogue. The modifications sit at opposite ends of the chain and are not interchangeable. In the same study the acetylated peptide did not reproduce the protection against copper(II) induced cell toxicity seen with the free-amine peptide, so treating this variant as a longer-lasting Semax is not supported by the chemistry.

A methodology caveat applies throughout. The coordination findings come from potentiometry, spectroscopy and one neuroblastoma line, the stability findings from incubation in biological media, and neither measures central nervous system activity.

Sealed lyophilized N-Acetyl Semax is stored at -20°C, shielded from light, in the unopened container. No duration is asserted here: the stability window for a batch is documented on its Certificate of Analysis.

Lyophilized material is hygroscopic, meaning it takes up atmospheric moisture, so a container reaches ambient temperature before opening. Freeze-thaw cycling is avoided. Methionine is the oxidation-sensitive residue and the histidine imidazole makes the chain pH-responsive.

Reconstitution is the term for returning a lyophilized compound to solution; this page defines the term and gives no procedure. N-Acetyl Semax sits in the aqueous solubility class, marginally less polar than the parent because acetylation removes one ionisable group.

Solid material is handled in low humidity with minimal open-container exposure. Short peptides adsorb to glass and plastic at low concentration, a recognised source of apparent loss. Preparation parameters belong to the cited methodology and the lot COA.

Identity and purity for this heptapeptide are established by reverse-phase high-performance liquid chromatography and mass spectrometry. Verified purity is documented per lot on the Certificate of Analysis.

Two checks are specific to this variant. The acetylated free acid and the acetylated amidate differ by about one mass unit, so an observed mass is read against the stated form, not the name. The second is that acetylation is present at all, since unmodified Semax sits roughly 42 units lower. Counter-ion content and residual water set fill weight against net peptide, recorded on the COA.

N-Acetyl Semax is catalogued with short peptides studied in central nervous system models.

• Semax.
  The unmodified parent and the source of nearly all data quoted around this compound.
• N-Acetyl Selank.
  The same acetylation on the other Russian heptapeptide stocked here.
• Selank.
  A tuftsin analogue using the same Pro-Gly-Pro stabilising tail.
• P21.
  A designed peptidomimetic, the other route to proteolytic stability.

Shevchenko KV, Nagaev IY, Andreeva LA, et al. (2013). Stability of Semax acetyl to proteolysis in biological media. Dokl Biol Sci.
PubMed 23652441

Magri A, Tabbi G, Giuffrida A, et al. (2016). Influence of N-terminus acetylation of Semax on copper(II) and zinc(II) coordination. J Inorg Biochem.
PubMed 27586814

Dergunova LV, Dmitrieva VG, Filippenkov IB, et al. (2021). ACTH(4-7)PGP (Semax) suppresses mRNA transcripts after reversible ischemia of the rat brain. Mol Biol (Mosk).
PubMed 34097675

Kolbaev SN, Sharonova IN, Skrebitsky VG (2025). Effect of peptide Semax on intracellular calcium dynamics in rat brain neurons. Bull Exp Biol Med.
PubMed 41171324

Peptides.com lists one N-Acetyl Semax research product, a sealed lyophilized vial from Verified Peptides at a 30mg fill. That per-vial strength is a product specification, not a research quantity. Vials are the only listed format for this variant; the parent is also stocked as a liquid spray. Each lot ships with a published Certificate of Analysis.

• Browse all N-Acetyl Semax research products
• Verified Peptides N-Acetyl Semax, 30mg lyophilized vial

These products are sold for Research Use Only and are not intended for human consumption.