Neuropeptide Analogues

Semax is Met-Glu-His-Phe-Pro-Gly-Pro, the ACTH(4-7) sequence extended with Pro-Gly-Pro to slow degradation. Selank is Thr-Lys-Pro-Arg-Pro-Gly-Pro, the immunomodulatory tetrapeptide tuftsin with the same C-terminal extension. Dihexa is a hexanoyl-capped dipeptide derivative of angiotensin IV. DSIP is a nonapeptide first isolated from rabbit brain. Cerebrolysin is not a single compound: it is a hydrolysate of porcine brain proteins containing low-molecular-weight peptides and free amino acids, so it has no single sequence, formula or CAS number.

Semax studies report changes in BDNF and TrkB expression in cultured neurons and brain tissue. Selank studies examine GABA-A receptor modulation and enkephalinase inhibition. Dihexa binds hepatocyte growth factor and is studied as a potentiator of HGF signalling through the c-Met receptor, measured by receptor phosphorylation and dendritic spine formation in neuronal culture. For DSIP no receptor has been identified.

Identity is established by mass spectrometry: an intact mass, or a precursor and fragment transition (MRM) matched against a reference standard, confirms that the sequence in the vial is the one on the label. Purity is a chromatographic figure, the principal peak area by reversed-phase HPLC, and it bounds peptide-related impurities only; it says nothing about counterion, water or residual solvent content, which is why net peptide content is reported separately. Lyophilised material is stored cold, dry and dark, and a certificate states what was measured on one named lot. Semax contains methionine and is therefore prone to oxidation, which shows up as a +16 Da species beside the main mass. A hydrolysate such as Cerebrolysin cannot be described by a single purity figure; it is characterised by its peptide size distribution and amino acid composition instead.

Much of the Semax and Selank literature comes from Russian institutions and is published in Russian-language journals, often with small samples; check whether a finding has been reproduced elsewhere. Dihexa has a short and narrow publication record. Be careful with studies of preparations that are mixtures, where an effect cannot be attributed to one molecule.