# Livagen > Livagen is a synthetic tetrapeptide with the sequence Lys-Glu-Asp-Ala (KEDA), a short peptide bioregulator modeled on peptide complexes from liver tissue. It has been studied mainly in cultured lymphocytes from elderly donors and patients, where it was reported to decondense chromatin and reactivate ribosomal genes. Peer-reviewed data come from a small group of laboratories, and it is not an FDA-approved drug. Canonical: https://peptideproperties.com/compounds/livagen/ ## Identity - **Class:** Short Peptide Bioregulators - **Also known as:** Lys-Glu-Asp-Ala - **Molecular formula:** C18H31N5O9 - **Molecular weight:** 461.5 g/mol - **Monoisotopic mass:** 461.2122 Da - **CAS number:** 433257-50-2 - **PubChem CID:** 87919683 - **InChIKey:** IKVDKWACACMDLR-BJDJZHNGSA-N - **Sequence:** KEDA - **Sequence notes:** Free N-terminal amine and free C-terminal carboxylic acid; no modifications. ## Key facts - Class: short peptide bioregulator (synthetic tetrapeptide) - Sequence: Lys-Glu-Asp-Ala (KEDA), four L-amino acids with free termini - Origin: synthesized from the composition of liver peptide complexes; stimulates liver explant growth - Formula C18H31N5O9; molecular weight 461.5 g/mol (PubChem CID 87919683) - CAS 433257-50-2 - Evidence base: almost entirely in-vitro studies of human lymphocytes and rat tissue explants - Regulatory status: not FDA approved; no approved medical indication in the United States ## What Is Livagen? Livagen is a synthetic tetrapeptide, Lys-Glu-Asp-Ala (KEDA), studied as a short peptide bioregulator that alters chromatin structure in cultured human cells. Its sequence is confirmed in several research papers.[1][2]Livagen belongs to the group of synthetic peptides, sometimes called cytogens, that Vladimir Khavinson and colleagues designed from the composition of tissue peptide complexes. In rat organotypic cultures, livagen stimulated the growth of liver explants, the tissue whose peptide complexes were used as the model for its synthesis, while related peptides stimulated their own tissues of origin.[3] The source complexes are referred to in that work as cytomedins, and the synthetic peptides modeled on them as cytogens.[3]Most subsequent research has examined livagen's effects on chromatin and chromosome stability in lymphocytes from elderly people and from patients with atherosclerosis, hypertrophic cardiomyopathy and breast cancer.[4][1][5] ## Chemical Structure and Molecular Identity Livagen is a linear peptide of four L-amino acids, lysine, glutamic acid, aspartic acid and alanine, with a free amine at the N-terminus and a free carboxylic acid at the C-terminus. PubChem (CID 87919683) lists the molecular formula C18H31N5O9 and a molecular weight of 461.5 g/mol.The sequence combines one basic residue (lysine) with two acidic residues (glutamate and aspartate) and a small neutral C-terminal alanine. PubChem's computed XLogP of -7.7 indicates very high water solubility and low lipophilicity, typical of short charged peptides. ### Key identifiers - CAS number: 433257-50-2 - InChIKey: IKVDKWACACMDLR-BJDJZHNGSA-N - Synonyms: Lys-Glu-Asp-Ala, KEDA, L-lysyl-L-glutamyl-L-aspartyl-L-alanineLivagen differs by one residue from other tetrapeptides in the same family. Its sequence should be distinguished from Lys-Glu-Asp-Gly, which carries glycine rather than alanine at the C-terminus and is a separate compound. The name livagen refers only to the free tetrapeptide, not to longer protein sequences that contain a KEDA motif. ## Research History and Development Livagen emerged from the Russian short-peptide program around 2000 and has since been studied mainly by cytogenetics researchers working with human lymphocyte cultures.A 2001 paper by Khavinson reported that the synthetic peptides cortagen, epitalon, livagen and vilon each stimulated explant growth in a tissue-specific way in rat organotypic cultures, with livagen acting on liver tissue.[3] A 2002 study then described its effects on ribosomal genes and heterochromatin in lymphocytes from old people.[4] That paper was co-authored by Khavinson and Lezhava, linking the original peptide program with the cytogenetic research that followed.From 2006 onward, a group led by Lezhava and Jokhadze, publishing largely in Georgian Medical News, compared livagen with epitalon and vilon and tested it alone and combined with cobalt ions in lymphocytes from aged donors and from patients with several diseases.[6][7][8] These studies are cell-culture experiments rather than treatment studies in people. ## Mechanisms Studied in Research The main mechanism proposed for livagen is chromatin reactivation: decondensation of heterochromatin that becomes more tightly packed with age, which may release silenced genes. Evidence comes from cytogenetic studies of cultured lymphocytes. ### Ribosomal gene activation These studies use classical cytogenetic methods, including measurement of ribosomal gene activity, thermal denaturation of heterochromatin, polymorphism of C-heterochromatin and variability of facultative heterochromatin.[4] In lymphocytes from old people, livagen activated ribosomal genes, decondensed pericentromeric structural heterochromatin and released genes repressed by age-related condensation of euchromatic regions.[4] A comparative study in lymphocytes from people aged 75 to 88 found that epitalon, livagen and vilon all reactivated ribosomal genes through decondensation of nucleolus organizer regions.[6] ### Structural heterochromatin Livagen and epitalon, but not vilon, induced decondensation of pericentromeric structural heterochromatin on chromosomes 1 and 9.[6] In lymphocytes from patients with hypertrophic cardiomyopathy and their relatives, livagen combined with cobalt ions increased the frequency of large nucleolar organizer regions and of associations between acrocentric chromosomes, which the authors interpreted as decondensation of heterochromatinized chromatin.[2] ### Radiation adaptive response One study examined the adaptive response, in which a small priming exposure to gamma radiation makes cells more resistant to a later damaging exposure. Lymphocytes from people aged 72 to 86 kept this adaptive capacity, priming radiation stimulated an adaptive response to copper chloride damage, and the authors reported a corrective effect of livagen in this system.[9] ### Interaction with cobalt In lymphocytes from donors aged 80 to 91, cobalt chloride alone raised chromosomal aberrations, and livagen reduced the number of cobalt-induced changes. Cobalt alone and cobalt with livagen shifted sister chromatid exchanges to different chromosome regions: pericentromeric heterochromatin with cobalt alone, and telomeric heterochromatin with the combination. The same study found that heterochromatinization, the condensation of chromosome regions, increased progressively with age and was linked to inactivation of previously active genes, which provides the rationale for testing a chromatin-decondensing peptide.[7] ## Key Findings From Published Studies Published livagen findings are almost entirely in-vitro, from cultured human lymphocytes and rat tissue explants; no animal treatment studies or clinical trials of livagen appear in the indexed abstracts reviewed here. ### Lymphocytes from elderly donors - Livagen activated ribosomal genes and decondensed structural and facultative heterochromatin.[4][6] - In lymphocytes from donors aged 80 to 91, livagen reduced chromosomal changes induced by cobalt chloride.[7] - In cells from people aged 72 to 86 exposed to low-level gamma radiation followed by copper chloride, cells retained a radiation adaptive response, and the authors reported a corrective effect of livagen.[9] ### Lymphocytes from patients - Atherosclerosis: lymphocytes from patients with atherosclerosis showed high genomic instability regardless of age. In these cells, livagen alone and with cobalt ions was reported to normalize altered indicators of genomic instability, a set of measures that included chromosome aberrations, aneuploidy and polyploidy, in both age groups studied.[1] - Breast cancer: lymphocytes from patients with ductal breast cancer showed many DNA single-strand breaks, frequent chromosomal abnormalities and increased chromatin condensation. Livagen and cobalt ions, used as modifying agents, had a protective effect across all of these measures.[5] - Hypertrophic cardiomyopathy: lymphocytes from patients and their first-degree relatives had more spontaneous chromosomal disorders than cells from healthy people. Among the peptides tested, epitalon, rather than livagen or vilon, showed the strongest effect in lowering chromosomal instability.[8] ### Tissue explants - In rat organotypic cultures, livagen stimulated the growth of liver explants specifically.[3]Some authors describe these lymphocyte results as evidence for disease prevention, but the experiments measured cytogenetic markers in cultured cells and did not test outcomes in patients.[1]Because livagen differs from related tetrapeptides by a single residue, researchers typically confirm identity with HPLC and mass spectrometry certificates of analysis. ## Regulatory and Research Status Livagen is not approved by the US Food and Drug Administration for any medical use and has no approved indication in the United States. It is available as a research chemical and remains an investigational peptide.The literature is small and concentrated in a few laboratories, and many papers are available only with brief English abstracts. Many studies combine livagen with cobalt ions, which makes the peptide's independent contribution harder to isolate.[2][5]Key gaps include the absence of published animal treatment studies, pharmacokinetic data and controlled human trials in the abstracts reviewed. Whether the chromatin changes seen in cultured lymphocytes occur in living tissue has not been established. The abstracts also do not report safety or toxicity data for livagen itself. ## FAQ **What is livagen made of?** Livagen is a tetrapeptide made of four amino acids: L-lysine, L-glutamic acid, L-aspartic acid and L-alanine, in that order (Lys-Glu-Asp-Ala, or KEDA). It has a free N-terminal amine and a free C-terminal carboxylic acid with no modifications. PubChem lists its formula as C18H31N5O9. **What is the molecular weight of livagen?** PubChem lists livagen (CID 87919683) with a molecular weight of 461.5 g/mol and the molecular formula C18H31N5O9. Its CAS number is 433257-50-2. These values refer to the free tetrapeptide rather than a salt form such as an acetate. **Is livagen FDA approved?** No. Livagen is not approved by the US Food and Drug Administration for any medical use and has no approved indication in the United States. It is sold as a research chemical and has been studied mainly in cultured human lymphocytes and rat tissue explants. **What does the research on livagen show?** Research on livagen is almost entirely in vitro. In cultured lymphocytes from elderly donors, it activated ribosomal genes and decondensed heterochromatin. In lymphocytes from patients with atherosclerosis or breast cancer, it was reported to reduce markers of genomic instability. No animal treatment studies or clinical trials appear in the indexed literature reviewed. **How is livagen different from epitalon?** Livagen is Lys-Glu-Asp-Ala, while epitalon is Ala-Glu-Asp-Gly. Both are tetrapeptides from the same research program. In lymphocytes from elderly donors, both decondensed pericentromeric heterochromatin on chromosomes 1 and 9. In lymphocytes from hypertrophic cardiomyopathy patients, epitalon showed a stronger effect on chromosomal instability than livagen. ## References 1. Dzhokhadze TA, Buadze TZh, Gaiozishvili MN, et al. [Genomic instability in atherosclerosis]. Georgian medical news 2014. PMID: 25541832 2. [Effect of peptide bioregulator and cobalt ions on the activity of NORs and associations of acrocentric chromosomes in lymphocytes of patients with hypertrophic cardiomyopathy and their relatives]. Georgian medical news 2014. PMID: 25341254 3. Khavinson VK. Tissue-specific effects of peptides. Bulletin of experimental biology and medicine 2001. PMID: 11713572 4. Khavinson VKh, Lezhava TA, Monaselidze JG, et al. Effects of Livagen peptide on chromatin activation in lymphocytes from old people. Bulletin of experimental biology and medicine 2002. PMID: 12533768 5. Jokhadze T, Gaiozishvili M, Buadze T, et al. [EVALUATION OF GENOMIC PARAMETERS IN DUCTAL BREAST CANCER PATIENTS AND THE ABILITY OF IT'S CORRECTION]. Georgian medical news 2017. PMID: 28574395 6. Lezhava T, Monaselidze J, Kadotani T, et al. Anti-aging peptide bioregulators induce reactivation of chromatin. Georgian medical news 2006. PMID: 16705247 7. Lezhava T, Jokhadze T. Activation of pericentromeric and telomeric heterochromatin in cultured lymphocytes from old individuals. Annals of the New York Academy of Sciences 2007. PMID: 17460203 8. Dzhokhadze TA, Buadze TZh, Gaĭozishvili MN, et al. [Functional regulation of genome with peptide bioregulators by hypertrophic cardiomyopathy (by patients and relatives)]. Georgian medical news 2013. PMID: 24423684 9. Dzhokhadze TA, Buadze TZh, Dvalishvili NA, et al. [Variability of radiation-induced adaptive response in old age individuals and their correction by Peptide bioregulator -Livagen]. Georgian medical news 2007. PMID: 17921545