Semax is a synthetic heptapeptide derived from the ACTH(4-7) fragment of adrenocorticotropic hormone, extended at the C-terminus with a proline-glycine-proline (Pro-Gly-Pro) sequence that confers marked resistance to enzymatic breakdown. The result is a short, chemically defined peptide whose stability far exceeds that of its unmodified parent fragment.
The ACTH-derived core
The active core reproduces a short segment of the ACTH sequence (commonly described as the 4-7 or 4-10 region) that lacks the classic hormonal, corticosteroid-releasing activity of full ACTH. This decoupling of the sequence from the parent hormone's endocrine role is central to why the peptide is studied as a distinct research tool rather than an ACTH mimic.
The Pro-Gly-Pro tail
Appending a Pro-Gly-Pro extension at the C-terminus is the defining modification. Prolines impose conformational rigidity and, together with the terminal arrangement, shield the peptide from carboxypeptidase cleavage. This greatly extends its in-vitro half-life while preserving the ACTH-derived core — the structural basis of its mechanism of action.
A short designed sequence
With only seven residues, Semax is a compact, fully synthetic sequence. The exact order of residues, and the placement of the stabilizing tail, entirely determine its identity; the general importance of residue order is covered in understanding amino acid sequences.
Solid-phase synthesis
Its short length makes Semax well suited to standard Fmoc solid-phase peptide synthesis. The chain is assembled residue by residue on a resin support, then cleaved and deprotected. Short sequences like this are routinely accessible to conventional synthesizers with high fidelity.
Purification, lyophilization, and QC
After synthesis, the peptide is purified by reversed-phase chromatography to remove truncated byproducts, then converted to a stable dry powder by freeze-drying (what is lyophilization). Final identity and purity are confirmed by HPLC and mass spectrometry, with the results recorded on a certificate of analysis (how to read a COA). Broader context is in the Semax research overview.
Stability must still be measured
The Pro-Gly-Pro tail improves resistance to some proteolytic routes, but it does not make the peptide chemically indestructible. Solution pH, temperature, light exposure, repeated handling, and microbial contamination can all affect a short peptide preparation. Laboratory stability is therefore established by time-point analysis rather than inferred from sequence alone. HPLC can reveal emerging degradation peaks, while mass spectrometry can help assign altered species. Because Semax and related short fragments differ by only a few residues, a complete sequence record and an unambiguous analytical match are essential for distinguishing the intended heptapeptide from truncated or closely related products.
Product page: Semax research vials.
Research Use Only. Supplied strictly for laboratory research and development — not for human or veterinary use, consumption, or any therapeutic or diagnostic purpose. This article is research education, not usage guidance.