Semax: structure, nomenclature and handling

The sequence is methionine–glutamate–histidine–phenylalanine–proline–glycine–proline, written MEHFPGP in single-letter code. It is a heptapeptide with a molecular weight of approximately 814 daltons.

The first four residues correspond to positions 4 through 7 of adrenocorticotropic hormone, a 39-residue peptide — the fragment conventionally written ACTH(4-7). The remaining three are the tripeptide proline–glycine–proline, which does not appear at that position in the parent and was added.

The reason for adding it is structural. Proline is the one amino acid whose side chain closes back onto its own backbone nitrogen, and a proline at the amino side of a bond makes that bond a poor substrate for most peptidases — enzymes that cleave ordinary chains stall at proline. Flanking a glycine with prolines therefore caps the carboxyl end of the molecule against exopeptidase attack. It is the same logic as the D-amino acid and acyl-group substitutions used elsewhere in this catalogue: leave the region of interest untouched and armour the vulnerable terminus.

The composition worth noting for handling is the methionine at position 1, a sulphur-containing residue and the most oxidation-prone in the standard amino acid set.

The material is catalogued as Semax, and in fragment notation as ACTH(4-7)-Pro-Gly-Pro or Met-Glu-His-Phe-Pro-Gly-Pro. It carries CAS 80714-61-0. As with most short synthetic peptides, it is typically isolated as an acetate salt, which affects the mass weighed out without altering identity.

An N-acetylated variant appears in catalogues as N-acetyl Semax, and a further variant extends that construct with an amidated amino acid at the carboxyl terminus. Both are distinct compounds with distinct masses: the acetyl group adds a defined 42-dalton increment, so the certificate's stated theoretical mass identifies which construct a batch is. Listings using the bare name for an acetylated variant are imprecise in a way the mass resolves.

Mass spectrometry confirms the intact molecular mass near 814 daltons. For this sequence the measurement also reports on oxidation state: an oxidized methionine adds a defined sixteen-dalton increment, so a batch carrying the sulfoxide form shows a satellite mass above the target. The absence of that satellite is part of what a clean identity result asserts.

High-performance liquid chromatography resolves the main peak from related substances and yields the purity figure. A seven-residue synthesis produces few deletion sequences, so the profile is usually simple; the compound-specific related substance is the methionine sulfoxide, which separates from the unoxidized peptide and typically elutes close to the main peak. Reading the chromatogram near the main peak against the mass data is how the two methods corroborate one another here.

One detail follows from the composition: the single phenylalanine gives only weak absorbance at the 280-nanometre wavelength used to quantify aromatic-rich peptides, so quantitation generally relies on backbone absorbance near 214 nanometres instead.

HEEZ Research supplies Semax in a single format: a 10 mg lyophilized vial. There is no second strength in the current catalogue, so the format decision that arises with two-size products does not apply here.

The material is supplied as a lyophilized powder. Freeze-drying removes water and leaves the peptide as a solid, markedly more stable than the same peptide in solution, and stable enough at ambient temperature to ship without refrigeration in transit.

Reconstitution converts the dried cake into a working solution, and it is a standard laboratory step rather than a product specification. Which solvent is used, and at what final concentration, is determined by the protocol in force at the receiving facility.

What HEEZ specifies is the contents of the vial: lyophilized Semax in a single 10 mg format, stated on the label and on the batch certificate of analysis. Where a protocol is expressed in molar rather than mass terms, the additional figure it needs is the molecular weight, which the certificate records for the batch supplied.

A seven-residue chain with two prolines is conformationally stiff and presents very little surface for aggregation. It dissolves readily in aqueous media, and vigorous agitation is unnecessary and avoided as a matter of routine.

Sealed lyophilized Semax is ambient-stable for the duration of transit, so no cold chain or insulated packaging is required for shipping. On receipt the vial goes to refrigeration and is kept out of direct light.

Reconstituted material is held refrigerated and used within the window the receiving facility's protocols specify, and repeated freeze-thaw cycling is avoided. Solutions are treated as short-lived relative to the lyophilized form.

The methionine is the residue that governs storage discipline. Oxidation to the sulfoxide proceeds in solution in the presence of dissolved oxygen and is accelerated by trace metals, so keeping the material dry until needed, limiting the number of times the vial is opened, and making solutions up fresh all matter more here than for a sequence without a sulphur-containing residue. The proline capping that resists enzymatic cleavage in biological media confers no advantage at all against this route.

The certificate records what an independent facility measured for one specific batch. Its value lies in being batch-specific, so the first check is that the lot number on the document matches the vial in hand.

The identity section compares observed molecular mass against a stated theoretical mass, which should sit near 814 daltons for the unmodified heptapeptide — not the acetylated variant 42 daltons heavier, and with no sulfoxide satellite sixteen daltons above.

The purity figure is the HPLC main-peak area as a percentage of total peak area, and the attached chromatogram shows how that figure was arrived at. Peaks sitting close to the main peak on this compound are most plausibly oxidized forms, and a batch analysed promptly after synthesis should show little of them.

Peptide content, or net peptide content, is sometimes reported separately. It accounts for counter-ions and residual water, and it is the figure determining how much actual peptide a nominal 10 mg represents.