Cortagen

Cortagen is a synthetic tetrapeptide, Ala-Glu-Asp-Pro, from the Khavinson short-peptide bioregulator programme. It differs from the neighbouring tripeptide Cartalax by a single C-terminal proline.

The sequence is stated in five independent primary sources, which for this class of compound is unusually solid: the US patent 7,189,701 claims it as H-Ala-Glu-Asp-Pro-OH, and papers by Anisimov and Khavinson in Neuroendocrinology Letters in 2004, by Kazakova and colleagues and by Khavinson and colleagues in the Bulletin of Experimental Biology and Medicine in 2002, and by Kuznik and colleagues in 2008 all name it with the same four residues.

Two identity confusions surround this compound and both are worth settling on the page. The first is with Cortexin, which is not a synonym: Cortexin is a polypeptide preparation extracted from cattle brain cortex with a mass around ten kilodaltons and an undefined composition, and Cortagen is the fully synthetic tetrapeptide that Anisimov and Khavinson designed from the amino-acid analysis of it. Data for one cannot be carried onto the other. The second is tissue: vendor pages variously attribute this peptide to brain cortex, to cartilage and to connective tissue, and the primary literature is consistent that it is the brain-cortex peptide. The cartilage attribution belongs to Cartalax, which is one residue away and routinely cross-labelled.

Both termini are unmodified. The formula and mass are for the free acid, from PubChem CID 18439621 and stated independently in the patent, which also records a melting point of 154 degrees Celsius and a specific rotation of minus 78.9 degrees measured in water. The isolated substance in the patent is an acetate and its stoichiometry is not stated, so no salt-adjusted mass follows from the figure here.

No CAS number is printed. One circulates, but its only source is a supplier deposit on PubChem with no curated registry heading behind it.

There is no tryptophan, tyrosine or phenylalanine, so there is no chromophore at 280 nm; the patent's own chromatography runs at 200 nm. There is no cysteine and no methionine, and no receptor has been identified for this compound.

The published molecular work is transcriptional and includes a negative result, which is reported here alongside the positive ones because leaving it out would misdescribe the literature. Anisimov, Khavinson and Anisimov ran a complementary-DNA microarray across 15,247 transcripts in murine heart tissue and reported significant change in 234 clones matching 110 known genes. Kazakova and colleagues reported activation of interleukin-2 messenger RNA synthesis in cultured murine splenocytes without a specific inductor, and noted it as less potent than two neighbouring peptides. Khavinson and colleagues, in the same year, found no comitogenic effect on murine thymocyte blast transformation and a weaker effect on membrane sphingomyelinase activity than the comparator peptides.