This is a working overview of freeze-thaw cycle, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2025-08-29. Anything still debated is marked as such rather than presented as settled.
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.
Clinical evidence comes mainly from small studies conducted in Russia, several of which were open-label or lacked robust blinding. Reported outcomes include lower anxiety scores, changes in attention measures, and effects on asthenic states following illness. Sample sizes are typically in the tens of participants, and independent replication outside the region is scarce. Reviews published in English generally note the limited methodological quality of the underlying trials. Whether the compound produces clinically meaningful effects under rigorous conditions remains unresolved.
Proposed mechanisms center on modulation of the GABA system, but no single molecular target has been confirmed. Rodent studies report changes in GABA-A receptor expression and in the turnover of serotonin, dopamine, and norepinephrine in several brain regions. Increases in brain-derived neurotrophic factor and its receptor have also been described after repeated administration. These findings come largely from animal models, and the degree to which they describe human neurochemistry remains an open question. The mechanism is best characterized as multi-system and not fully resolved.
| Property | Value | Notes |
|---|---|---|
| Chemical class | Synthetic heptapeptide | Tuftsin analogue with a C-terminal Pro-Gly-Pro tail |
| Amino acid sequence | Thr-Lys-Pro-Arg-Pro-Gly-Pro | Abbreviated TKPRPGP in most catalogues |
| Molecular mass | About 752 Da | Value for the free peptide |
| Solubility | Freely soluble in water | Aqueous solutions are kept cold and used promptly |
| Typical storage | -20 °C, dry, protected from light | Applies to the lyophilised powder before reconstitution |
Pharmacokinetic data are sparse and largely derived from animal work. After intranasal administration the peptide appears in plasma within minutes, and reported half-lives are short, on the order of minutes to tens of minutes. Degradation proceeds through ordinary proteolytic cleavage into constituent amino acids and smaller fragments. Direct evidence that intact Selank reaches brain tissue in meaningful amounts is limited, and the extent of blood-brain barrier penetration is debated. Some authors argue that fragments, not the parent peptide, carry much of the observed activity.
Published clinical work is concentrated in Russian-language journals and generally involves small samples without independent replication. Systematic reviews in English note the shortage of randomised, placebo-controlled trials and the difficulty of verifying methods from translated reports. Outcome measures vary between studies, which complicates pooling of results. Interest in the compound as a cognitive or anxiolytic agent therefore rests on a thinner evidence base than the volume of citations suggests. Replication in well-powered trials with preregistered endpoints would be needed before firm conclusions about efficacy can be drawn.
Identity and purity of selank are established with reversed-phase high-performance liquid chromatography coupled to mass spectrometry. The peptide elutes from C18 columns with acetonitrile gradients in water containing trifluoroacetic acid or formic acid, and detection is usually performed by ultraviolet absorbance near 214 nm. Electrospray ionization in positive mode gives a doubly protonated ion near m/z 377, consistent with a mass of about 752 Da. Amino acid analysis or tandem mass spectrometry of fragment ions confirms the sequence. Because the molecule has no aromatic residues, it lacks a usable 280 nm chromophore, so low-wavelength detection or mass spectrometry is required.
Peptide bonds in selank are susceptible to hydrolysis under strongly acidic or basic conditions, and the terminal proline residues are vulnerable to exopeptidase activity in biological samples. Lyophilized powder stored dry at -20 °C typically remains stable for extended periods, whereas aqueous solutions degrade faster and may lose measurable purity within days to weeks depending on pH, temperature, and microbial load. Repeated freeze-thaw cycles promote aggregation and adsorption to container surfaces. For analytical work, solutions are usually prepared fresh, kept cold, and used within a single working day.
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.
Most published work on selank originates from a small number of research groups in the Russian Federation. A large share of that record appears in Russian-language journals, which limits access for readers who rely on English-indexed databases. Independent replication by laboratories outside the original research network is sparse in publicly available sources. This concentration of origin and language is a frequently noted feature when the compound is summarized in broader reviews of synthetic peptides.
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.
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==== Prognosis ==== Patients typically improve over time without additional antibiotics, but this may take several months or years. There is a lack of long-term data, with few studies of symptoms more than 12 months from initial infection; however, PTLDS symptoms may anecdotally remain for years or even decades.
The mammalian gut microbiome has emerged as a key regulator of host physiology, and coevolution between host and microbial lineages has played a key role in the adaptation of mammals to their diverse lifestyles. Diet, especially herbivory, is an important correlate of microbial diversity in mammals. Most mammalian microbiomes are also strongly correlated with host phylogeny, despite profound shifts in diet. This suggests host factors that themselves change across host phylogeny, such as gut physiology, play an important role in structuring the gut microbiomes across mammals. The vertebrate adaptive immune system is even speculated to have evolved as just such a factor for selective maintenance of symbiotic homeostasis. The importance of phylogeny-correlated factors to the diversity of vertebrate microbiomes more generally is still poorly understood. Phylosymbiosis, or the observation that more closely related host species have more similar microbiomes, has been described in a number of nonmammalian taxa. Other analyses have found substantial variation in phylosymbiotic signals among mammalian taxa, sometimes with conflicting results. The presence of a robust phylosymbiotic correlation implies that host factors control microbial assembly. Even if the specific mechanisms are unknown, variation in the strength or presence of a measurable phylosymbiotic signal across host phylogeny could prove useful for identifying such mechanisms through comparative studies.
Sources: en.wikipedia.org
Culp came to national attention early in his career as the star of the 1957–1959 CBS Western television series Trackdown, in which he played Texas Ranger Hoby Gilman, based in the town of Porter, Texas. It was one of Culp's many appearances in TV Westerns. The pilot for Trackdown was "Badge of Honor", a 1956 episode of Dick Powell's Zane Grey Theatre, in which Culp starred as Gilman. In 1960, he appeared in two more episodes of Zane Grey Theatre, playing different roles in "Morning Incident" and "Calico Bait". After Trackdown ended in 1959 after two seasons, Culp continued to work in television, including a guest-starring role as Stewart Douglas in the 1960 episode "So Dim the Light" of CBS's anthology series The DuPont Show with June Allyson. In the summer of 1960, he guest-starred on David McLean's NBC Western series Tate. He played Clay Horne in the series finale, "Cave-In", of the CBS Western Johnny Ringo, starring Don Durant. In 1961, Culp played the part of Craig Kern, a morphine-addicted soldier, in the episode "Incident on Top of the World" in the CBS series Rawhide. About this time, Culp was cast on the NBC anthology series, The Barbara Stanwyck Show and in the NBC Civil War drama, The Americans. Culp was cast as Captain Shark in a first-season episode of NBC's The Man from U.N.C.L.E. (1964). Some of his more memorable performances were in three episodes of the science-fiction anthology series on The Outer Limits (1963–1965), including the classic "Demon with a Glass Hand", written by Harlan Ellison.
== Manufacturing == The vaccine candidate can be made in a lyophilized powder form, allowed it to be shipped and stored between 2 and 8 °C (36 and 46 °F). In August 2021, Arcturus Therapeutics entered a partnership with Vinbiocare, a unit of Vingroup to conduct clinical trials of ARCT-154 COVID-19 vaccine, developed created using Arcturus’ STARR mRNA technology, in Vietnam and establish a manufacturing facility a factory in Hòa Lạc Hi-tech Park, Hanoi, which requires an estimated investment of $200 million and has the capacity to make 200 million doses per year. It is expected that Vingroup will produce its first batches of the vaccine in early 2022. Arcturus will provide to Vinbiocare access to "proprietary technologies and processes for the manufacture" of its vaccines, as well as an exclusive license to manufacture them solely for sales and use in Vietnam. This includes all of Arcturus’ other Covid-19 vaccines such as ARCT-021 and other vaccines in the future for disease prevention in Vietnam. Vinbiocare will pay $40m upfront, be responsible for technology transfer costs, and "pay for mRNA drug substance supplied by Arcturus and royalties on vaccines produced at the facility".
=== Relations with Tibet === In the fall of 1933, the 13th Dalai Lama sent an ultimatum to Liu Wenhui stating that Tibet would launch another attack if the 24th Army did not retreat further east. The ultimatum was not followed up because of the Lama's death on 17 December. In the wake of the ensuing political instability within the region, Liu cabled Nanjing for an expeditionary force to restore Chinese control over the entirety of Tibet. However, Dai Jitao and other close advisors to Chiang Kai-shek chose a more conciliatory policy and urged restraint on 23 December, which Liu Wenhui again ignored. Here, historian James Leibold speculates that Liu would probably have seized Lhasa had it not been for his untimely defeat at the hands of his nephew. In 1934, the new Tibetan government of Jamphel Yeshe Gyaltsen was ready to pursue peace with the central government, as the war with Liu had drained the monasteries' resources and driven up the price of Chinese tea. Chiang dispatched General Huang Musong on a diplomatic mission to Lhasa, with the aim of getting Tibet to accept Chinese sovereignty in exchange for broad autonomy. This mission, although accepted by the Kashag, was foiled when Liu Wenhui met with Huang in Chengdu and urged a hard line on the border issue. This was anathema to the Tibetans who wanted a demilitarized buffer zone in Xikang to protect from Liu Wenhui's army.
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Sources: en.wikipedia.org
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.
Tuftsin is a natural tetrapeptide derived from the Fc portion of immunoglobulin G. Selank retains that tetrapeptide at its N-terminus and adds three residues to improve resistance to enzymatic breakdown. The relationship is structural, and the two molecules are not interchangeable in experimental work.
It holds a product registration in Russia for intranasal use as an anxiolytic. Registrations of that kind are not automatically accepted by regulators elsewhere. In most other countries it is treated as an unapproved substance or a research material.
Reports describe effects on GABA-A receptor expression, monoamine turnover, and neurotrophic factor levels. These are proposed mechanisms drawn mainly from animal models. No single molecular target has been established.