Semax

The Pro-Gly-Pro strategy

The first four residues — Met-Glu-His-Phe — are positions 4-7 of adrenocorticotropic hormone. On its own that tetrapeptide is degraded very quickly by aminopeptidases. The appended Pro-Gly-Pro tail is the entire design: proline-containing motifs are poor peptidase substrates, and the C-terminal extension markedly increases the fragment’s survival in biological media.

Selank uses the same tail on an entirely different parent sequence, which makes the pairing a design pattern rather than a coincidence.

The methionine at position 1

This is the single most important handling fact about Semax. Methionine oxidizes to the sulfoxide at +16 daltons, and an N-terminal residue is maximally exposed to solvent and oxygen. A mass spectrum of aged Semax commonly shows a +16 satellite.

Practical consequences: store lyophilized, cold, dark and desiccated; reconstitute in degassed buffer where feasible; consider low-concentration EDTA to chelate the trace metals that catalyse the reaction; and do not leave solutions at room temperature. Amber vials genuinely earn their cost for this peptide, since the phenylalanine adds photosensitivity alongside the methionine.