Selank

Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) is a synthetic heptapeptide developed at the Institute of Molecular Genetics of the Russian Academy of Sciences, combining the tuftsin immunomodulatory tetrapeptide (Thr-Lys-Pro-Arg) with a Pro-Gly-Pro C-terminal stability extension. Registered as a pharmaceutical in Russia and Ukraine following clinical research, Selank is classified as a research compound outside these jurisdictions and is supplied by Signal Labs for laboratory and analytical research purposes only.

The research rationale for Selank begins with its parent compound tuftsin — a naturally occurring tetrapeptide (Thr-Lys-Pro-Arg) cleaved from the Fc region of immunoglobulin G by a specific enzyme (tuftsin endocarboxypeptidase) on splenic macrophages. Tuftsin activates a specific receptor on macrophages and neutrophils, stimulating phagocytosis, superoxide production, and microbicidal activity. By incorporating the complete tuftsin sequence at positions 1-4 and adding the Pro-Gly-Pro C-terminal stability extension, Selank was designed as a metabolically stabilised tuftsin analogue with potentially extended pharmacological activity.

The Pro-Gly-Pro tripeptide at positions 5-7 contributes multiple properties: C-terminal carboxypeptidase resistance (terminal Pro is a poor carboxypeptidase A substrate), independent bioactivity as a leukocyte chemotactic factor and ECM-derived signalling peptide, and improved aqueous solubility relative to the shorter tuftsin sequence. The Arg-Pro-Gly-Pro C-terminal sequence is particularly resistant to carboxypeptidase degradation due to the proline preceding the terminal residue — many carboxypeptidases cannot cleave X-Pro bonds.

Selank's published neurobiological research profile includes GABAergic signalling modulation. In vitro electrophysiology studies and competitive binding data have examined Selank's interactions with GABA-A receptor complexes, with published data suggesting modulation of the benzodiazepine binding site or allosteric sites on GABA-A receptors in brain membrane preparations. Anxiolytic-like behavioural effects in rodent models (elevated plus maze, open field test, social interaction) have been reported in published Russian research and attributed partly to GABAergic enhancement.

Enkephalin system research has examined whether Selank inhibits enkephalin-degrading enzymes: neprilysin (neutral endopeptidase, CD10) cleaves the Gly3-Phe4 bond of Met-enkephalin and Leu-enkephalin; aminopeptidase M (CD13) cleaves the Tyr1-Gly2 bond. Published research has used fluorometric enzyme assay to assess whether Selank concentrations that produce behavioural effects in rodent models can inhibit neprilysin activity in brain membrane preparations — a mechanism that would extend endogenous opioid peptide half-lives without directly activating opioid receptors.

BDNF expression research has examined Selank's effects on BDNF mRNA and protein in hippocampal cell models, with published data suggesting upregulation at concentrations in the nanomolar range. If confirmed, this BDNF-elevating effect would parallel Semax's BDNF biology — providing a rationale for the Semax+Selank combination blend that covers both ACTH/BDNF (Semax) and GABAergic/opioidergic (Selank) neurochemical pathways simultaneously.

For GABAergic research with Selank: whole-cell patch-clamp of cultured hippocampal neurons (DIV14-21). In voltage clamp at -70mV, record spontaneous IPSCs (sIPSCs) in the presence of glutamate receptor antagonists (DNQX 10uM + AP5 50uM) to isolate GABAergic events. Apply Selank (1nM-1uM) by bath perfusion and measure changes in sIPSC amplitude, frequency, and decay kinetics versus vehicle. Flumazenil pre-treatment (benzodiazepine site antagonist, 1uM) tests whether Selank acts at the benzodiazepine binding site. For enkephalin system research: use radiolabelled substrate-based neprilysin activity assay — incubate brain membrane preparation with fluorogenic substrate (e.g., dansyl-Gly-Gly-Phe-Leu) in the presence of Selank (1nM-100uM) and measure fluorescence development over time versus neprilysin inhibitor thiorphan control. MW: 863.0 g/mol. CAS: 129954-34-3. Reconstitute in bacteriostatic water at 1mg/mL. Store lyophilised at -20°C. For laboratory and analytical research purposes only.