Selank

Selank has the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. The first four residues are tuftsin, a tetrapeptide corresponding to a segment of the immunoglobulin G heavy chain constant region, released from it by proteolysis. The final three residues, Pro-Gly-Pro, are a synthetic extension appended to the tuftsin core.

That extension is a stability design rather than a targeting element. Proline residues at and near the C-terminus are poor substrates for carboxypeptidases and for most aminopeptidase-directed trimming, so the extension slows degradation of a tetrapeptide that would otherwise be cleared within minutes. Three of the seven residues are proline, giving the backbone unusually restricted conformational freedom.

No dedicated receptor has been identified. The mechanistic literature describes interaction with GABAergic signalling and modulation of enkephalin-degrading enzyme activity, which are pathway-level observations rather than a defined binding target, and they should be read as such.

Enzyme activity work is the most direct line of evidence. Enkephalin-degrading enzyme activity is assayed in rodent brain and plasma preparations, with reported inhibition proposed to prolong the lifetime of endogenous enkephalins rather than to act at any receptor directly.

Other reported endpoints include GABA-A receptor subunit expression and binding in rodent brain tissue, monoamine and metabolite turnover measured by HPLC with electrochemical detection in brain homogenates, and interleukin and interferon transcript levels in cultured cells, the last of these connecting back to the immunomodulatory origins of the tuftsin core. As with the related peptide bioregulators, a substantial part of the primary literature originates from a small number of groups and is published in Russian-language journals.

Two features of the sequence complicate routine analysis. First, it contains no tryptophan, tyrosine or phenylalanine, so there is no absorbance at 280 nanometres and detection has to run at 210 to 220 nanometres on the peptide bond, a channel in which buffer components and residual solvents also absorb.

Second, three prolines mean slow cis-trans isomerisation about the preceding amide bonds. On a reversed-phase column this produces broadened, shouldered or split peaks that look like impurities and are not. Running the column at elevated and controlled temperature accelerates interconversion and collapses the peaks together, which is why a proline-rich peptide analysed at ambient temperature can appear less pure than the same lot analysed at 40 degrees. A lot report for this compound should state the column temperature.

Mass spectrometry confirms the sequence without ambiguity. With one lysine and one arginine against no acidic residue the peptide is strongly basic, so it is supplied as a salt and net peptide content differs from chromatographic purity by the counterion and water fraction.