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Background And Chemical Identity — Deep Dive

By Editorial Desk · published 2026-03-01 · last reviewed 2026-04-03 · News

If you have been reading about tetrapeptide and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.

Updated 2026-04-03. Numbers and descriptions here follow the published literature rather than marketing material.

Background and Chemical Identity

Several names circulate for the same molecule, including epitalon, epithalone, epithalamin tetrapeptide, and the sequence code AEDG. A CAS registry number, 307297-39-8, is commonly cited for it, though catalogue entries should be checked against supplier documentation because mislabelled records occur. In its usual form the peptide carries free amino and carboxyl termini and is neither glycosylated nor lipidated. Researchers distinguish the defined tetrapeptide from epithalamin itself, a crude pineal preparation containing many peptides that is not chemically characterised.

Material supplied for laboratory use is normally a lyophilised white to off-white powder that dissolves readily in water and in isotonic saline. Lyophilised cakes are hygroscopic and should be equilibrated to room temperature before opening to limit condensation on the solid. Solutions are typically prepared at milligram-per-millilitre concentrations and divided into single-use aliquots, because repeated freeze–thaw cycles degrade short peptides. Aqueous solutions are far less stable than the dry powder, and identity is usually verified by mass spectrometry alongside purity estimation from reversed-phase high-performance liquid chromatography.

Epitalon is a synthetic linear tetrapeptide with the sequence alanine–glutamate–aspartate–glycine, abbreviated AEDG. Its molecular formula is C14H22N4O9 and the calculated mass is approximately 390.35 g/mol. The compound is made by solid-phase peptide synthesis rather than extracted from tissue, although early work described it as a short fragment of a peptide fraction obtained from bovine pineal extract. In the research literature the spelling epitalon and the variant epithalone both appear, while AEDG is the standard code used in peptide nomenclature.

Analytical Characterization and Stability

Because epitalon has no pharmacopoeial monograph, quality assessment depends on supplier documentation and independent testing. Certificates of analysis typically report a purity figure from a single chromatographic run, a measured mass and sometimes an appearance description, but methods and acceptance criteria are not harmonised across vendors. Third-party laboratories can repeat identity and purity measurements, and mismatches between labelled and measured peptide content have been described for research peptides generally. What constitutes adequate identity confirmation for a molecule of this size stays an open question, since mass agreement alone does not separate closely related sequences.

Identity testing for epitalon relies on reversed-phase high-performance liquid chromatography for purity and mass spectrometry for mass confirmation. Because the sequence contains no tryptophan or tyrosine, ultraviolet detection at 280 nanometres is insensitive, so chromatographic methods usually monitor absorbance near 214 nanometres, where the peptide backbone absorbs. Electrospray ionisation or matrix-assisted laser desorption/ionisation then checks the intact mass against the expected value near 390 daltons. Peptide mapping or amino acid analysis after acid hydrolysis can supplement these measurements, although such confirmatory work is seldom reported on commercial certificates of analysis.

Stability of the tetrapeptide follows ordinary peptide chemistry rather than any unusual structural feature. The aspartate-glycine pair is prone to aspartimide formation under mildly basic or neutral conditions, and deamidation can follow, altering both mass and chromatographic retention. Dry lyophilised powder kept at or below minus twenty degrees Celsius is the usual handling recommendation, with repeated freeze-thaw cycles avoided. Once dissolved in neutral aqueous buffer, degradation proceeds over days to weeks depending on pH and temperature, while acidic conditions generally slow the aspartimide route. A formal stability-indicating study has not been published in the indexed literature.

Epitalon at a glance

PropertyValueNotes
Amino acid sequenceAla-Glu-Asp-GlyLinear tetrapeptide, also written AEDG
Molecular massAbout 390.35 g/molValue calculated from the sequence
AppearanceWhite to off-white powderLyophilised material forms a loose cake
SolubilityFreely soluble in waterAlso dissolves in isotonic saline
Storage-20 °C, desiccatedAliquot solutions to avoid freeze–thaw cycling

Chemical Identity and Research Background

The compound is described in the literature as a derivative of epithalamin, a preparation obtained from bovine pineal tissue. Work on this peptide family was carried out mainly by a research group in Saint Petersburg beginning in the 1980s, and the substance was later registered for clinical use in Russia under the name Epitalon. Outside that region it is generally treated as a research chemical rather than an approved medicine. Statements about its biological activity rest on a relatively small number of studies, and independent replication remains limited.

In its supplied form epitalon is a white to off-white powder, usually lyophilized and often hygroscopic. It dissolves readily in water and in aqueous buffers, and it is commonly handled as the acetate or trifluoroacetate salt to improve stability during purification and drying. The amide backbone is labile in aqueous media, so solutions are less durable than the dry solid. Handling notes in the chemical literature therefore emphasize keeping the powder dry, cool and shielded from light until it is dissolved.

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Laboratory Handling and Analytical Verification

Short peptides such as AEDG are normally supplied as a freeze-dried solid and are kept dry, cold, and shielded from light. Holding at minus twenty degrees Celsius is common for the long term, while a refrigerator suffices for brief periods before use. The material takes up moisture to some degree, so containers should stay sealed and be allowed to reach room temperature before opening, which limits condensation on the contents. Repeated warming and cooling of a single container is discouraged because it admits water and can lower the amount of intact peptide.

Dissolution is usually performed in water or a suitable aqueous buffer, and the resulting liquid is divided into single-use portions before freezing. Freeze-thaw cycling is a recognised source of loss for short peptides, since each cycle can encourage aggregation or adsorption onto container walls. Working solutions are generally kept cold and used within a short window, although published stability data specific to epitalon are thin. Containers should be marked with concentration and date, and solutions examined for cloudiness before use.

Structure, Naming and Discovery

The compound is generally described as a synthetic analogue of a fragment isolated from a pineal gland extract. Researchers associated with the Saint Petersburg Institute of Bioregulation and Gerontology introduced it during the 1980s and 1990s while studying short peptides from animal tissue. The original extract, called epithalamin, is a heterogeneous mixture, whereas epitalon is a single defined sequence. That distinction matters because findings reported for the extract are not automatically findings about the pure tetrapeptide, and claims about broader biological effects remain a separate question from the chemical identity described here.

Residue composition is the property that most cleanly separates verified material from mislabelled samples. Alanine, glutamate, aspartate and glycine appear in that order from the N-terminus, and the two acidic residues sit in the middle of the chain. Because the peptide is short, it can be produced by solid-phase synthesis and characterised by mass spectrometry without ambiguity. Any reported sample whose measured mass departs substantially from 390 daltons is a different compound or a degraded mixture rather than epitalon.

Epitalon is a synthetic tetrapeptide whose four residues are alanine, glutamate, aspartate and glycine, commonly abbreviated AEDG. Its molecular formula is C14H22N4O9 and its monoisotopic mass is near 390.35 daltons. The peptide carries two acidic side chains, so it is neutral to negatively charged in most aqueous buffers. Published reference summaries usually list it under both spellings, epitalon and epithalon, and treat the two names as the same material.

Further detail

Individuals in professions such as pilots, nuclear physicians, and nuclear power plant workers are regularly exposed to ionizing radiation. In Germany, over 400,000 workers undergo occupational radiation monitoring to safeguard against the harmful effects of radiation. Approximately 70,000 individuals employed across various industries possess a radiation pass (distinct from an X-ray pass - see below). Individuals who may receive an annual effective dose of more than 1 millisievert during their work are required to undergo radiation protection monitoring. In Germany, the effective dose from natural radiation is 2.1 millisieverts per year. Radiation dose is measured using dosimeters, and the occupational dose limit is 20 millisieverts per year. Monitoring also applies to buildings, plant components or (radioactive) substances. These are exempted from the scope of the Radiation Protection Ordinance by a special administrative act, the exemption in radiation protection. To this end, it must be ensured that the resulting radiation exposure for an individual member of the public does not exceed 10 μSv per calendar year and that the resulting collective dose does not exceed 1 person sievert per year.

=== Inhibition of ACTH production === Corticotropes contain glucocorticoid receptors (GRs) and corticosteroid-binding globulin (CBG, or transcortin). GR is a nuclear receptor that inhibits transcription of ACTH via a negative glucocorticoid recognition element (GRE) that binds cortisol on POMC DNA, but generally transcortin binds glucocorticoids (including cortisol, cortisone, deoxycortisone, and aldosterone) with high affinity and prevents this inhibition. Tonic inhibition of corticotropes requires high concentrations of glucocorticoids, exceeding CBG capacity. This causes ACTH secretion to be vulnerable to inhibition in patients taking glucocorticoids for medical purposes such as treatment of autoimmune disease or as an anti-transplant-rejection medication.

==== Crf-dynorphin-kor cascade ==== Diverse stressors initiate CRF release which subsequently leads to dynorphin release and KOR activation in limbic circuits. This integrated stress response is mediated primarily by corticotropin-releasing factor (CRF), one of the main neuropeptide integrators of the stress response. Physical stressors trigger CRF release from the hypothalamic paraventricular nucleus (PVN). Cold exposure provokes CRF secretion from the hypothalamus and produces increases in plasma glucocorticoids. Acute physical stressors such as forced swimming, inescapable footshock, and restraint stress similarly lead to CRF release. Acute stress induces rapid increases in plasma corticosterone levels that are dependent on CRF secretion. Intravenous CRF administration induces rapid increases in KOR phosphorylation in striatal, VTA, amygdaloid, hippocampal, and nucleus accumbens (NAcc) components of stress and anxiety circuits. These CRF-induced increases are absent in prodynorphin (PDYN) knockout mice. Social defeat stress model activates CRF and dynorphin. Learned helplessness also engages these systems. Fear conditioning and fear-related stress produce KOR-dependent behavioral responses through CRF receptor. The uncontrollability and inescapability of the stressor substantially augments the response. Even brief, non-intensive stressors produce significant neurobiological and behavioral effects when unpredictable and uncontrollable, whereas identical stressors with controllability demonstrate attenuated activation of stress systems.

In May 2004, the United States Court of Appeals for the Federal Circuit vacated the previous judgment by the US District Court for the Northern District of Illinois, and the case was remanded back for further court proceedings. Teva continued to sell its generic during this time. The patent for Vicoprofen expired on 18 December 2004, officially opening the drug to generic manufacture. In July 2016, the FDA approved another generic equivalent, manufactured by Aurobindo Pharma Limited.

The new name was proposed after 70% of a panel of experts expressed support for this name. This new name was adopted in 2023. Formerly, abnormal accumulation of fat in the liver in the absence of secondary causes of fatty liver, such as significant alcohol use, viral hepatitis, or medications that can induce fatty liver, was the definition of NAFLD. However, the term MASLD accepts that there may be other conditions present, but focuses on the metabolic abnormalities contributing to the disorder.

Sources: en.wikipedia.org

Background from the literature

=== Depression === The primary use of trazodone is the treatment of unipolar major depression with or without anxiety. Data from open and double-blind trials suggest that the antidepressant efficacy of trazodone is comparable to that of amitriptyline, doxepin, and mianserin. Furthermore, trazodone has shown anxiolytic properties, low cardiotoxicity, and relatively mild side effects. Because trazodone has minimal anticholinergic activity, it was especially welcomed as a treatment for geriatric patients with depression when it first became available. Three double-blind studies reported trazodone had antidepressant efficacy similar to that of other antidepressants in geriatric patients. Unfortunately, a side effect of trazodone, orthostatic hypotension, may cause dizziness and increase the risk of falling. This may have devastating consequences for elderly patients. Therefore, this side effect, along with sedation, often makes trazodone less acceptable for this population compared to newer compounds that share its lack of anticholinergic activity (but not the rest of its side effect profile). Still, trazodone is often helpful for geriatric patients with depression who have severe agitation and insomnia. Trazodone is usually used at a dosage of 150 to 300 mg/day for the treatment of depression. Lower doses have also been used to augment other antidepressants or when initiating therapy. Higher doses, up to 600 mg/day, have been used in more severe cases of depression (in hospitalized patients, for example).

This interpretation remained controversial until NMR techniques demonstrated information transfer between hydrogen-bonded nuclei, a feat that would only be possible if the hydrogen bond contained some covalent character.

Selecting the linear velocity is therefore the same compromise between the level of separation and length of analysis as selecting the column temperature. The linear velocity will be implemented by means of the carrier gas flow rate, with regards to the inner diameter of the column. With GCs made before the 1990s, carrier flow rate was controlled indirectly by controlling the carrier inlet pressure, or "column head pressure". The actual flow rate was measured at the outlet of the column or the detector with an electronic flow meter, or a bubble flow meter, and could be an involved, time consuming, and frustrating process. It was not possible to vary the pressure setting during the run, and thus the flow was essentially constant during the analysis. The relation between flow rate and inlet pressure is calculated with Poiseuille's equation for compressible fluids. Many modern GCs, however, electronically measure the flow rate, and electronically control the carrier gas pressure to set the flow rate. Consequently, carrier pressures and flow rates can be adjusted during the run, creating pressure/flow programs similar to temperature programs.

Biomatrica, Inc. is a United States-based biotechnology company, and subsidiary of Exact Sciences Corporation, that develops chemicals for ambient temperature preservation of biological materials for the purpose of expanding the availability and accuracy of medical diagnostics and research. Specifically, the company focuses on improving the stability of biological materials, such as DNA, RNA, proteins, cells from patient samples used in research, and diagnostic testing reagents. Company scientists have developed alternatives to existing preservation technologies, such as cold storage and lyophilization (freeze-drying), to prevent degradation of perishable biological materials. Biomatrica's technologies are used in applications such as pre-analytic sample collection, diagnostic assays, biobanking, forensics, and basic research.

Sources: en.wikipedia.org

Frequently asked questions

Is epitalon a natural substance?

It is a synthetic tetrapeptide. Its sequence was derived from research on peptide fractions of bovine pineal extract, and the intact AEDG sequence has not been demonstrated as an abundant free peptide in human tissue.

What does the abbreviation AEDG mean?

AEDG is the one-letter code for the four amino acids alanine, glutamate, aspartate and glycine in that order. The same molecule is written in three-letter form as Ala-Glu-Asp-Gly.

How is the identity of epitalon confirmed in a laboratory?

Identity is normally confirmed by mass spectrometry against the calculated mass of roughly 390.35 g/mol. Purity is then estimated by reversed-phase high-performance liquid chromatography with ultraviolet detection.

Why is ultraviolet detection at 214 nanometres used?

The molecule lacks aromatic residues, so it absorbs weakly near 280 nanometres, the wavelength applied to many other peptides. The peptide bond absorbs strongly below 220 nanometres, making 214 nanometres a practical compromise. Gradient methods must therefore use mobile phases with low ultraviolet absorbance to keep the baseline clean.

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