What Is Semax? Structure, Chemistry and the Published Research

What Semax is

Semax is a synthetic peptide of seven amino acid residues with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. It encompasses sequence 4 to 7 of the N-terminal domain of adrenocorticotropic hormone (ACTH) followed by a C-terminal Pro-Gly-Pro tripeptide.^[1] In the literature it is usually described as an analogue of the ACTH fragment 4 to 10.^[2]

That makes it a fragment-derived design, not a hormone in its own right. The same Pro-Gly-Pro tail appears in Selank, which the Selank primer describes. The sequence can be written out and checked by anyone with a table of residue masses, which is the starting point for every identity check described below.

Chemistry at a glance

The molecular formula listed for the Sealed Peptides product is C37H51N9O10S and the listed molecular weight is 813.9 Da. Adding up average atomic masses for that formula gives 813.93 g/mol, so the formula and the listed weight agree. The monoisotopic mass of the same formula is 813.348, and the singly protonated ion that a mass spectrometer would be expected to report is therefore near m/z 814.36. The monoisotopic and average figures answer different questions, as the mass spectrometry guide explains.

Four features of the sequence shape how it behaves on the bench. It contains methionine, a sulfur-containing residue whose oxidation in solution has been studied in detail for other methionine-containing molecules.^[3] See oxidation in the glossary. It contains no cysteine, so there is no disulfide bond to consider. It has one acidic residue (glutamate) and one histidine, and no lysine or arginine. And it has a free amino terminus and a free carboxyl terminus; an N-terminally acetylated version, Ac-Semax, has been studied as a separate chemical entity and differs in its metal-binding chemistry.^[1]

What the published literature describes

Everything below comes from in-vitro or animal studies, and it is summarized here as description, not as a finding about any use.

Binding and breakdown. In a study of rat forebrain membranes, labelled Semax bound specifically, reversibly and in a calcium-dependent way, with a dissociation constant of about 2.4 nM. The same study followed its degradation by HPLC and reported that dipeptidyl aminopeptidases are the main enzymes responsible, cleaving Semax stepwise to the pentapeptide His-Phe-Pro-Gly-Pro and then to the tripeptide Pro-Gly-Pro, with a half-life in the presence of the membranes longer than one hour.^[4]

Gene expression in rats. A single application of Semax was reported to change BDNF protein and trkB phosphorylation in rat hippocampus, along with BDNF and trkB mRNA.^[2] A separate in-vivo study found rapid, gene- and region-specific changes in neurotrophin gene expression in normal rat brain: BDNF expression rose in the hippocampus, brainstem and cerebellum, while NGF expression fell in the frontal cortex.^[5]

Transcriptome analysis. In a rat model of experimental brain ischemia, a genome-wide study compared tissue from Semax-exposed and control animals and found that the largest group of altered genes was related to the immune system, with a smaller group related to the vascular system.^[6]

Metal coordination. Semax and its acetylated form have been characterized as ligands for copper(II) and zinc(II). Acetylation changed the copper complex that formed, and the free amino terminus was reported to matter for protection against copper-induced toxicity in a neuroblastoma cell line.^[1]

What that literature cannot tell you

These studies were done in rats, mice and cell systems under conditions chosen by the authors. They describe changes in molecules such as mRNA and protein levels; they do not establish what Semax does in any other organism or setting, and nothing here describes or endorses any use of the material. Several of the abstracts also use clinical language about the compound. That language is the authors’, and it is deliberately not repeated on this page.

The research overview at Semax research overview lists the compound’s cited literature in the same descriptive way.

Analytical notes for the bench

Identity is usually confirmed by mass: an observed m/z compared with the expected value, and fragment ions that match the sequence. Purity is usually reported as the share of the total peak area in a HPLC chromatogram. Each answers a separate question, and neither measures how much peptide is in a weighed powder; that is the net peptide content question.

Detection depends on the residues. Semax has no tryptophan, tyrosine or cystine, which are the three groups that account for absorbance at 280 nm,^[7] so it absorbs little there. At 214 nm, phenylalanine and histidine each absorb roughly six times as strongly as the peptide bond, and a proline inside the chain absorbs about three times as strongly,^[8] which is why 214 nm is the practical wavelength. Semax has one phenylalanine, one histidine and two prolines.

Methionine oxidation has been studied in solution kinetics for another methionine-containing molecule. In that work light exposure, storage temperature and oxygen content had a considerable impact on the oxidation rate.^[3] It is a reason to keep the oxidation question in mind when reading an HPLC trace, not a prediction for any particular preparation. The storage and degradation guide covers the wider picture.