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Origins And Proposed Mechanisms — Field Notes

By Editorial Desk · published 2026-07-10 · last reviewed 2026-08-01 · Guide

This is a working overview of Enkephalinase, written for readers who want more than a one-paragraph summary but less than a textbook.

This page was last updated on 2026-08-01 and is reviewed periodically as new material appears.

Origins and Proposed Mechanisms

Published clinical evidence is limited. Most controlled trials were conducted in Russia, enrolled modest numbers of participants, and appeared in Russian-language journals, which restricts independent verification. Reported outcomes include lower anxiety scores, improved attention and memory measures, and changes in fatigue ratings. Reviews written in English note methodological limitations such as small samples and inconsistent endpoints. Whether the compound produces clinically meaningful benefit relative to established anxiolytics is therefore an open question rather than an established finding.

Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. It was designed at the Institute of Molecular Genetics of the Russian Academy of Sciences as a structural analogue of tuftsin, a naturally occurring tetrapeptide fragment of the immunoglobulin heavy chain. The added Pro-Gly-Pro tail was intended to slow enzymatic degradation and extend biological activity. In Russia it is registered as an anxiolytic nasal preparation, while regulators elsewhere have not approved it for clinical use.

Background and Molecular Identity

Development took place at the Institute of Molecular Genetics of the Russian Academy of Sciences, where a series of short peptides were designed in the 1980s and 1990s. Selank was selected from variants of tuftsin that showed resistance to plasma peptidases. Russian regulatory approval covers it as an anxiolytic agent given intranasally. Outside that market the compound is normally handled as a research chemical rather than a medicine, and no widely recognised international pharmacopoeial monograph exists. The name Selank is a coined trade designation rather than a systematic chemical name.

Enzymatic stability motivates the extra three residues at the carboxyl end. Native tuftsin is cleaved quickly by circulating aminopeptidases and carboxypeptidases, which limits its duration of action and its usefulness as a tool compound. Extending the chain with proline-rich segments is a common design tactic because proline constrains the backbone and slows proteolysis. The same Pro-Gly-Pro motif appears in other Russian-developed peptides of the era. Whether the full seven-residue chain is required for activity, or whether it acts mainly as a prodrug releasing tuftsin, remains unresolved.

Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. Its four N-terminal residues reproduce tuftsin, a tetrapeptide fragment of the immunoglobulin heavy chain, while the C-terminal Pro-Gly-Pro extension is a synthetic addition. The peptide has a molecular mass near 752 daltons and carries a net positive charge at physiological pH because of the arginine and lysine side chains. Published indexes list it under the name Selank and the sequence abbreviation TKPRPGP. Solid-phase peptide synthesis is the standard production route for research quantities.

Selank at a glance

PropertyValueNotes
Molecular formulaC33H57N11O9Free peptide form
Molecular massAbout 751.9 DaCalculated average mass
Amino acid sequenceThr-Lys-Pro-Arg-Pro-Gly-ProSingle-letter form TKPRPGP
Structural basisTuftsin analogueExtended version of a natural tetrapeptide
Development originRussian Academy of SciencesWork carried out from the 1980s onward

Selank Background and Peptide Chemistry

Reported pharmacological effects center on reduced anxiety-like behavior in animal models and on measures of memory and learning. Proposed contributing mechanisms include modulation of GABAergic signaling, shifts in monoamine turnover, and changes in the activity of enzymes that degrade neuropeptides. Effects on the expression of genes linked to neuroplasticity have also been described. No single molecular target is widely accepted, and whether the behavioral findings arise from one pathway or several remains an open question.

Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. It was designed as a stabilized analogue of tuftsin, a naturally occurring tetrapeptide fragment derived from the immunoglobulin heavy chain. The additional Pro-Gly-Pro segment at the carboxyl terminus is intended to slow enzymatic cleavage. The compound is usually described in the literature as a synthetic peptide with anxiolytic and cognitive-related activity, a label that reflects a research context rather than an approved therapeutic category.

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Selank Background And Chemical Identity

The primary structure of Selank is Thr-Lys-Pro-Arg-Pro-Gly-Pro, corresponding to the molecular formula C33H57N11O9 and a monoisotopic mass of roughly 751.9 daltons. The N-terminal threonine and the arginine residue in the fourth position are shared with tuftsin, which carries the sequence Thr-Lys-Pro-Arg. The three additional residues at the C-terminus, Pro-Gly-Pro, extend the chain and are associated with greater resistance to enzymatic degradation. This extension also separates Selank from the shorter parent peptide.

Naming conventions place Selank in the same research family as Semax, another Russian-developed peptide investigated for cognitive effects. The two compounds share a lineage but differ in sequence and in the biological systems proposed as their targets. Semax descends from ACTH fragments, whereas Selank descends from tuftsin. Publications sometimes identify Selank by its full peptide sequence or by laboratory codes rather than one uniform trade name. Because replication outside Russia is limited, reports on its properties are best read alongside the study design and the purity of the material tested.

Selank Origin and Chemical Identity

Selank is a synthetic heptapeptide developed in Russia as a structural analogue of tuftsin, a naturally occurring immunomodulatory tetrapeptide. Its sequence, Thr-Lys-Pro-Arg-Pro-Gly-Pro, keeps the tuftsin core at the N-terminus and appends a Pro-Gly-Pro tail. Researchers at the Institute of Molecular Genetics in Moscow synthesized the compound during the 1990s while searching for peptides with combined anxiolytic and immunomodulatory activity. The added tail was intended to resist enzymatic cleavage and prolong the molecule's presence in circulation.

The compound has a calculated molecular weight near 751.9 daltons and carries a net positive charge at physiological pH because of its arginine residue. It dissolves freely in water and in common aqueous buffers, and typically appears as a white or off-white lyophilized powder. The amide backbone makes the molecule susceptible to peptidases, which limits oral use and favors intranasal or parenteral routes. Nomenclature in the literature varies: the substance is also described by the sequence abbreviation TP-7 and by a Russian trade designation.

Further detail

=== Indigenous peoples === The first inhabitants of North America are generally hypothesized to have migrated from Siberia by way of the Bering land bridge and arrived at least 14,000 years ago. The Paleo-Indian archaeological sites at Old Crow Flats and Bluefish Caves are two of the oldest sites of human habitation in Canada. The characteristics of Indigenous societies included permanent settlements, agriculture, complex societal hierarchies, and trading networks. Some of these cultures had collapsed by the time European explorers arrived in the late 15th and early 16th centuries and have only been discovered through archaeological investigations. Indigenous peoples in present-day Canada include the First Nations, Inuit, and Métis, the last being of mixed descent who originated in the mid-17th century when First Nations people married European settlers and their offspring subsequently developed their own identity. The Indigenous population at the time of the first European settlements is estimated to have been between 200,000 and two million, with a figure of 500,000 accepted by Canada's Royal Commission on Aboriginal Peoples. As a consequence of European colonization, the Indigenous population declined by forty to eighty percent. The decline is attributed to several causes, including the transfer of European diseases, to which they had no natural immunity, conflicts over the fur trade, conflicts with the colonial authorities and settlers, and the loss of Indigenous lands to settlers and the subsequent collapse of several nations' self-sufficiency.

Outside of the US, the drug thalidomide was marketed for the relief of general nausea and morning sickness, but caused birth defects and even the death of thousands of babies when taken during pregnancy. American mothers were largely unaffected as Frances Oldham Kelsey of the FDA refused to authorize the medication for market. In 1962, the Kefauver-Harris Amendment to the FD&C Act was passed, which represented a "revolution" in FDA regulatory authority. The most important change was the requirement that all new drug applications demonstrate "substantial evidence" of the drug's efficacy for a marketed indication, in addition to the existing requirement for pre-marketing demonstration of safety. This marked the start of the FDA approval process in its modern form. These reforms had the effect of increasing the time, and the difficulty, required to bring a drug to market. One of the most important statutes in establishing the modern American pharmaceutical market was the 1984 Drug Price Competition and Patent Term Restoration Act, more commonly known as the "Hatch-Waxman Act" after its chief sponsors. The act extended the patent exclusivity terms of new drugs, and tied those extensions, in part, to the length of the FDA approval process for each individual drug.

=== Long-overlap-based assembly === There have been a variety of long-overlap-based assembly methods developed in recent years. One of the most commonly used methods, the Gibson assembly method, was developed in 2009, and provides a one-pot DNA assembly method that does not require the use of restriction enzymes or integrases. Other similar overlap-based assembly methods include Circular Polymerase Extension Cloning (CPEC), Sequence and Ligase Independent Cloning (SLIC) and Seamless Ligation Cloning Extract (SLiCE). Despite the presence of many overlap assembly methods, the Gibson assembly method is still the most popular. Besides the methods listed above, other researchers have built on the concepts used in Gibson assembly and other assembly methods to develop new assembly strategies like the Modular Overlap-Directed Assembly with Linkers (MODAL) strategy, or the Biopart Assembly Standard for Idempotent Cloning (BASIC) method.

The endogenous α-amino acids L-leucine and L-isoleucine, which closely resemble pregabalin and the other gabapentinoids in chemical structure, are apparent ligands of the α2δ VGCC subunit with similar affinity as the gabapentinoids (e.g., IC50=71 nM for L-isoleucine), and are present in human cerebrospinal fluid at micromolar concentrations (e.g., 12.9 μM for L-leucine, 4.8 μM for L-isoleucine). It has been theorized that they may be the endogenous ligands of the subunit and that they may competitively antagonize the effects of gabapentinoids. In accordance, while gabapentinoids like pregabalin and gabapentin have nanomolar affinities for the α2δ subunit, their potencies in vivo are in the low micromolar range, and competition for binding by endogenous L-amino acids has been said to likely be responsible for this discrepancy. Pregabalin was found to possess 6-fold higher affinity than gabapentin for α2δ subunit-containing VGCCs in one study. However, another study found that pregabalin and gabapentin had similar affinities for the human recombinant α2δ-1 subunit (Ki=32 nM and 40 nM, respectively). In any case, pregabalin is 2 to 4 times more potent than gabapentin as an analgesic and, in animals, appears to be 3 to 10 times more potent than gabapentin as an anticonvulsant.

Sources: en.wikipedia.org

Supporting material

Initial oxidation to the ferric (Fe3+) state without oxygen converts hemoglobin into "hemiglobin" or methemoglobin, which cannot bind oxygen. Hemoglobin in normal red blood cells is protected by a reduction system to keep this from happening. Nitric oxide is capable of converting a small fraction of hemoglobin to methemoglobin in red blood cells. The latter reaction is a remnant activity of the more ancient nitric oxide dioxygenase function of globins.

Miscellaneous: Cellulose can be converted into cellophane, a thin transparent film. It is the base material for the celluloid that was used for photographic and movie films until the mid-1930s. Cellulose is used to make water-soluble adhesives and binders such as methyl cellulose and carboxymethyl cellulose which are used in wallpaper paste. Cellulose is further used to make hydrophilic and highly absorbent sponges. Cellulose is the raw material in the manufacture of nitrocellulose (cellulose nitrate) which is used in smokeless gunpowder. Pharmaceuticals: Cellulose derivatives, such as microcrystalline cellulose (MCC), have the advantages of retaining water, being a stabilizer and thickening agent, and in reinforcement of drug tablets.

== Medicine == Muscle contraction, the physiological condition of a muscle which generates tension (traction) at its origin and insertion Uterine contraction, contraction of the uterus, such as during childbirth Contractility, the intrinsic ability of the heart/myocardium to contract Wound contraction, a stage in wound healing

== Hazards == Radium is highly radioactive, as is its immediate decay product, radon gas. When ingested, 80% of the ingested radium leaves the body through the feces, while the other 20% goes into the bloodstream, mostly accumulating in the bones. This is because the body treats radium as calcium and deposits it in the bones, where radioactivity degrades marrow and can mutate bone cells. Exposure to radium, internal or external, can cause cancer and other disorders, because radium and radon emit alpha and gamma rays upon their decay, which kill and mutate cells. Radium is generally considered the most toxic of the radioactive elements. Some of the biological effects of radium include the first case of "radium-dermatitis", reported in 1900, two years after the element's discovery. The French physicist Antoine Becquerel carried a small ampoule of radium in his waistcoat pocket for six hours and reported that his skin became ulcerated. Pierre Curie attached a tube filled with radium to his arm for ten hours, which resulted in the appearance of a skin lesion, suggesting the use of radium to attack cancerous tissue as it had attacked healthy tissue. Handling of radium has been blamed for Marie Curie's death, due to aplastic anemia, though analysis of her levels of radium exposure done after her death find them within accepted safe levels and attribute her illness and death to her use of radiography. A significant amount of radium's danger comes from its daughter radon, which as a gas can enter the body far more readily than can its parent radium.

A 2004 meta-analysis of randomised controlled clinical trials that compared benzodiazepines to zopiclone or other Z drugs such as zolpidem and zaleplon has found few clear and consistent differences between zopiclone and the benzodiazepines in sleep onset latency, total sleep duration, number of awakenings, quality of sleep, adverse events, tolerance, rebound insomnia, and daytime alertness.

Sources: en.wikipedia.org

Supporting material

=== Indirect unknown mechanism === Two of the primary active constituents of the medicinal herb Hypericum perforatum (St. John's Wort) are hyperforin and adhyperforin. Hyperforin and adhyperforin are wide-spectrum inhibitors of the reuptake of serotonin, norepinephrine, dopamine, glutamate, GABA, glycine, and choline, and they exert these effects by binding to and activating the transient receptor potential cation channel TRPC6. Activation of TRPC6 induces the entry of calcium (Ca2+) and sodium (Na+) into the cell, which causes the effect through unknown mechanism.

=== Anesthesia === The use of ketamine in anesthesia reflects its characteristics. It is a drug of choice for short-term procedures when muscle relaxation is not required. The effect of ketamine on the respiratory and circulatory systems is different from that of other anesthetics. It suppresses breathing much less than most other available anesthetics. When used at anesthetic doses, ketamine usually stimulates rather than depresses the circulatory system. Protective airway reflexes are preserved, and it is sometimes possible to administer ketamine anesthesia without protective measures to the airways. Psychotomimetic effects limit the acceptance of ketamine; however, lamotrigine and nimodipine decrease psychotomimetic effects and can also be counteracted by benzodiazepines or propofol administration. Ketofol is a combination of ketamine and propofol. Ketamine is frequently used in severely injured people and appears to be safe in this group. It has been widely used for emergency surgery in field conditions in war zones, for example, during the Vietnam War. A 2011 clinical practice guideline supports the use of ketamine as a sedative in emergency medicine, including during physically painful procedures. It is the drug of choice for people in traumatic shock who are at risk of hypotension. Ketamine often raises blood pressure upon administration and is unlikely to lower blood pressure in most patients, making it useful in treating severe head injuries for which low blood pressure can be dangerous.

=== Other approved uses === GH can be used to treat conditions that produce short stature but are not related to deficiencies in GH. However, results are not as dramatic when compared to short stature that is solely attributable to deficiency of GH. Examples of other causes of shortness often treated with GH are Turner syndrome, Growth failure secondary to chronic kidney disease in children, Prader–Willi syndrome, intrauterine growth restriction, and severe idiopathic short stature. Higher ("pharmacologic") doses are required to produce significant acceleration of growth in these conditions, producing blood levels well above normal ("physiologic"). One version of rHGH has also been FDA approved for maintaining muscle mass in wasting due to AIDS.

Rowe, Federal Narcotics Laws and the War on Drugs: Money Down a Rat Hole. Binghamton, NY: Haworn Press, 2006. Eric Schneider, "The Drug War Revisited", Berfrois, November 2, 2011. Peter Dale Scott and Jonathan Marshall, Cocaine Politics: Drugs, Armies, and the CIA in Central America. Berkeley, CA: University of California Press, 1911. Dominic Streatfeild, Cocaine: An Unauthorized Biography. Macmillan, 2003. Douglas Valentine, The Strength of the Wolf: The Secret History of America's War on Drugs. New York: Verso, 2004.

Sources: en.wikipedia.org

Frequently asked questions

What is Selank made of?

It is a seven-amino-acid peptide, Thr-Lys-Pro-Arg-Pro-Gly-Pro, produced by chemical synthesis rather than extracted from biological tissue. Its design is based on tuftsin, a natural immunomodulatory tetrapeptide. The C-terminal Pro-Gly-Pro segment is a common stabilising motif in short regulatory peptides.

Is Selank a naturally occurring substance?

The core four residues correspond to tuftsin, which occurs naturally as part of immunoglobulin G. The full seven-residue sequence, however, is not a known endogenous peptide. It is a laboratory-designed analogue intended to combine tuftsin-like activity with greater resistance to breakdown.

Which receptors does it act on?

No single receptor has been confirmed as the primary target. Reports describe involvement of the GABAergic system, interference with enkephalin degradation, and shifts in neurotrophic factor expression. Because these observations come from different models and assays, they have not yet been integrated into one accepted mechanism.

What is Selank chemically?

Selank is a seven-amino-acid peptide built from the tuftsin sequence plus a Pro-Gly-Pro tail. It is produced by chemical synthesis rather than extracted from a natural source. The free peptide is usually supplied as a lyophilised powder or in an aqueous formulation.

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