N-Acetyl Selank Amidate

N-Acetyl Selank Amidate

N-Acetyl Selank Amidate is a modified form of the peptide Selank. Selank is a short nootropic and anxiolytic peptide originally developed in Russia. It is an analogue of naturally occurring tuftsin and has been shown to have immunomodulatory effects. Research suggests that Selank modifies gene expression in the brain, reducing the effects of the neurotransmitter GABA, altering cell membrane permeability, and enhancing production of brain-derived neurotrophic factor (BDNF). [1]

The modified form of Selank, N-Acetyl Selank Amidate has a longer half-life and greater ability to cross the blood-brain barrier. It also has tighter receptor binding due to the amidation. Selank is currently being researched in animal models for the treatment of stroke and other ischemic brain diseases. It is also under consideration as a treatment of generalized anxiety disorder and to protect memory in the setting of neurodegenerative disease.

N-Acetyl Selank Amidate Structure

Authoritative source：PubChem

Here in the sequence, “Ac-” represents the Acetyl group attached to the N-terminus of the peptide, and “-NH2” represents the Amidated group at the C-terminus. The amino acid sequence “TPRKEPV” corresponds to the core Selank peptide. Acetyl-Selank-Amidate is a modified version of Selank, a synthetic peptide with anxiolytic and immunomodulatory properties. The addition of the Acetyl and Amidated groups may enhance its stability, bioavailability, and efficacy.

N-Acetyl Selank Amidate and DNA

Selank exhibits various effects, especially within the central nervous system, which have captured the attention of scientists. Studies conducted by Dr. Anastasiya Volkova at the Institute of Molecular Genetics in Russia suggest that Selank achieves these effects by modulating gene expression. In essence, Selank has the ability to activate or suppress specific segments of DNA, thereby influencing the functioning of our bodies. Research conducted on rats demonstrates that Selank alters the activity of at least 52 different genes.

Selank and Anxiety

One of the most extensively studied properties of Selank is its capacity to regulate anxiety. Research indicates that Selank exhibits clinical effects similar to those of benzodiazepine drugs commonly used in the treatment of severe anxiety disorders. Selank has demonstrated effectiveness in reducing anxiety, alleviating stress, and enhancing mood. Its mechanism of action is believed to involve interaction with the GABA receptor, albeit likely through an indirect pathway, akin to benzodiazepines. Furthermore, Selank exhibits sedative effects comparable to those of benzodiazepines. [2]

Where Selank distinguishes itself from medications like Ativan and Valium is in its apparent lack of addictive properties. Benzodiazepines are notorious for their potential for abuse, along with the risk of physical dependence and addiction. In contrast, Selank does not seem to possess these concerns and, in fact, may prove beneficial in aiding individuals dependent on benzodiazepines to gradually and safely withdraw from them.

Research indicates that out of the 84 genes associated with GABA, Selank has the ability to modify at least 45 of them. As mentioned earlier, the impact of Selank on the GABAa receptor is believed to be indirect. It is hypothesized that instead of directly binding to the GABA receptor, Selank alters the receptor’s affinity for its natural ligand. This mechanism is believed to contribute to the reduction of anxiety by diminishing the effect of natural GABA without affecting its concentration.

Interestingly, Selank and conventional benzodiazepines have been studied in combination, and the use of both substances seems to yield better results in treating certain types of anxiety compared to using either one alone. Specifically, this combination has shown significant effectiveness in addressing the challenging and persistent form of anxiety known as unpredictable chronic mild stress.

Selank and the Blood-Brain Barrier

Selank belongs to the glyproline peptide family, which is recognized for its regulatory functions in biological systems. Glyprolines are renowned for their ability to provide protection and promote repair in various parts of the body[3]. The specific effects of glyprolines depend on the amino acid sequence of the individual glyprotein. While certain glyprolines exhibit activity in the gastrointestinal tract or pancreas, others, such as Selank, exert their effects in the central nervous system.

The glyproline family has generally received less attention in research settings. Nonetheless, some common characteristics of these highly stable oligopeptides have been identified. Of particular significance for Selank is their ability to traverse the blood-brain barrier. The blood-brain barrier (BBB) is a formidable barrier comprising cellular and extracellular components that restrict the passage of substances from the general circulation into the central nervous system. Compared to most other oligopeptides, glyprolines exhibit greater permeability across this barrier.

N-Acetyl Selank Amidate and the Immune System

According to Dr. Olga Uchakina, a recipient of a Rockefeller Foundation grant and affiliated with Mercer University School of Medicine, animal studies have demonstrated that Selank can suppress the production of the inflammatory cytokine IL-6. IL-6, or interleukin-6, is secreted by macrophages as well as cells in the bone marrow and blood vessels. It serves as an inflammatory marker for severe COVID-19 infection. IL-6 is involved in various functions, including the regulation of fever, neutrophil production, and B cell growth. Within the central nervous system, IL-6 is implicated in the consolidation of emotional memories during sleep and may act as a mediator of pain perception.[4] 

The modulation of IL-6 expression in the central nervous system and its potential impact on pain perception is particularly intriguing for researchers studying the interactions between IL-6 and Selank. Studies conducted on rats suggest that Selank may influence IL-6 expression in the central nervous system, potentially leading to a reduction in pain associated with asthenic symptoms[5]. The relationship between psychiatric conditions and physical pain has long been a subject of debate within the medical community. The ability of Selank to alleviate physical pain in psychiatric conditions seems to support the validity of this hypothesis while providing a potential solution. Currently, it remains unclear whether Selank can provide relief from other forms of neurogenic pain. Future research endeavors may shed light on the role of glyprolines as regulators of pain originating from the nervous system, thereby contributing to a better understanding of how to manage and treat neuropathic pain.

Selank as Anticoagulant

Extensive research has been conducted to explore the potential of Selank in the treatment and recovery of ischemic brain disease. A significant portion of this research has centered around Selank’s role as a gene regulator and its capacity to enhance neurogenesis. However, it has been discovered that Selank may offer additional benefits in the context of ischemic brain disease.

Animal studies have demonstrated that Selank (and Semax) can play a role in regulating the coagulation process (blood clotting). These peptides have the potential to maintain homeostasis in the coagulation cascade and counteract the effects of both hypercoagulation (excessive blood clotting) and, to a lesser extent, bleeding. Preliminary findings suggest that Selank may possess anti-coagulant properties. However, further research is necessary to fully understand this characteristic, which could position Selank as a dual therapeutic option in the context of stroke. In such cases, Selank could not only protect neurons against excitotoxic damage but also safeguard them from abnormal coagulation processes. [7]

Supporting the observations of Selank’s benefits in hypercoagulable states is research conducted on rat mesenteric vessels. This research demonstrates that Selank, in general, can help prevent microcirculation hypercoagulation occurring in mesenteric vessels due to immobilization. Consequently, glyprolines like Selank are garnering increasing interest for their potential to regulate coagulation cascades in cases of prolonged immobilization, often associated with surgery or hospitalization. Currently, blood clots resulting from such cases are treated with heparin injections, which can disrupt the balance and lead to bleeding. The ability of Selank and other glyprolines to regulate coagulation in a gentle manner, without inducing overcompensation or causing bleeding, makes them highly attractive for the development of blood clot prophylactics.

N-Acetyl Selank Amidate as Nootropic

No discussion of Selank would be complete without exploring its potential to enhance cognition. Extensive research has established a connection between Selank and alterations in gene expression patterns related to anxiety and coagulation. Moreover, further research conducted on rats demonstrates that the nasal administration of Selank leads to changes in mRNA levels for 36 different genes associated with plasma membrane function, as well as ion-dependent learning and memory functions.[2]

Rats treated with Selank demonstrate enhanced memory trace stability, leading to improved long-term retention of learning. Furthermore, Selank has shown the ability to restore memory and learning abilities in the aftermath of brain damage, under certain circumstances. It is believed that Selank can inhibit the catecholamine system in the brain, thereby counteracting excitotoxic neuron death. Excitotoxic neuron death is observed in various conditions such as head injury, drug overdose, and neurodegenerative diseases like Parkinson’s disease.

Administration of Selank in rats has been linked to elevated levels of BDNF, a neurotransmitter in the central nervous system that promotes the growth and differentiation of neurons. Increased BDNF levels are correlated with enhanced learning, improved memory, and mitigated effects of neurological damage. Various nootropics have been shown to modulate BDNF expression patterns in the brain. The enhanced ability of N-Acetyl Selank Amidate to penetrate the blood-brain barrier likely renders it a more potent nootropic compared to regular Selank.

The Purpose of N-Acetylation

N-Acetyl Selank Amidate exhibits similar effects to Selank, as discussed earlier, which raises the question of why modify the original compound. N-acetylation is a common modification found in natural peptides, particularly in eukaryotes. In fact, most proteins in our bodies undergo N-acetylation. In yeast and humans, N-acetylation serves multiple roles, including:

• Modifying protein-protein interactions.
• Influencing subcellular localization.
• Altering the three-dimensional folding of proteins.
• Affecting degradation rates.

In synthetic chemistry, N-acetylation is used to modify the charge, hydrophobicity, and size of a protein. This can impact the protein’s stability, its distribution within the body, and its binding to receptors. In most cases, N-acetylation is performed to extend the half-life of a protein without significantly affecting its overall function. It is a relatively straightforward process, making it a cost-effective and well-established approach to enhance the potency of a peptide.[4]

The Purpose of Amidation

Amidation is another peptide modification that occurs at the carboxyl group, located at the opposite end of the amino acid chain. Similar to N-acetylation, amidation is a natural process found in approximately half of all known peptides. Amidation renders peptides less susceptible to proteolytic degradation and prolongs their half-life in the bloodstream. Amidated peptides exhibit reduced sensitivity to pH changes and have a higher affinity for their receptors. They also exhibit stronger binding to their target receptors, thereby extending the effects of amidated proteins compared to their non-amidated counterparts. Natural peptides such as oxytocin, thyroid-releasing hormone, and vasopressin demonstrate significantly enhanced biological activity through amidation.[5]

In synthetic biology, amidation serves three primary functions. Firstly, amidation aids in the protection of orally administered peptides against the harsh environment of the stomach and gastrointestinal (GI) tract. The stomach’s acidic pH, which is typically below 2, poses a challenge for the survival of many peptides. The presence of an amide group enables proteins to pass through the stomach without degradation, reducing the quantity of peptide required to be consumed in order to achieve desired concentrations in the bloodstream.[6]

The second rationale for amidating synthetic peptides is to enhance their potency after absorption. Amidated proteins not only exhibit prolonged survival in the bloodstream but also bind more strongly to their target receptors, leading to enhanced signaling [12]. This aspect is especially significant for peptides with activity in the central nervous system, such as Selank. Although Selank demonstrates better penetration of the blood-brain barrier (BBB) compared to many other compounds, its ability to enter the central nervous system is still somewhat limited. By increasing the potency of the peptide, its effects in the CNS can be amplified and more pronounced.

Lastly, amidation also affects the lipid solubility of a compound. Although this function is not as pivotal as the previously mentioned ones, it is worth noting that amidation increases the compound’s lipid solubility, resulting in greater penetration of Selank across the blood-brain barrier (BBB). Therefore, amidated Selank not only exhibits enhanced potency through improved receptor binding but also enables a larger quantity of the peptide to reach the receptors in the central nervous system. In this case, the single process of amidation offers two distinct benefits that synergistically contribute to the overall effectiveness of Selank.

N-Acetyl Selank Amidate: Summary

N-Acetyl Selank Amidate can be regarded as an improved version of Selank, surpassing it in various aspects. N-Acetyl Selank Amidate enhances Selank’s potency, prolongs its half-life, improves its absorbability, and facilitates its passage across the blood-brain barrier. These enhancements contribute to the amplification of Selank’s effects, which have been observed in animal studies to include neuroprotective properties, anxiety reduction, enhanced learning and memory, and modulation of the coagulation process. While further research is necessary, the exploration of Selank and other glyprolines provides valuable insights into how a single peptide can modify DNA expression patterns to yield profound effects.