Vilon

What Is Vilon?

Vilon is the synthetic dipeptide L-lysyl-L-glutamic acid (Lys-Glu), studied as a short peptide bioregulator with immunomodulating and geroprotective activity in laboratory and animal models. It is one of the short peptides created at the St. Petersburg Institute of Bioregulation and Gerontology, which are described as regulating gene expression and protein synthesis.^[1]

Most vilon research has been carried out by Khavinson, Anisimov and colleagues. An early report described vilon as inhibiting the growth of spontaneous tumors and increasing lifespan in mice.^[2] Later studies examined its effects on thymus cells, chromatin in cells from elderly people, gene expression in heart tissue and recovery after irradiation.

Vilon is frequently studied side by side with epitalon (Ala-Glu-Asp-Gly), a tetrapeptide from the same program. The two are often tested in the same experiments, but their reported effects differ.^[3][4]

Chemical Structure and Molecular Identity

Vilon is a linear dipeptide in which the carboxyl group of L-lysine is joined by a peptide bond to the amine of L-glutamic acid, leaving a free N-terminal amine and a free C-terminal carboxylic acid. PubChem (CID 7010502) lists the molecular formula C11H21N3O5 and a molecular weight of 275.30 g/mol.

The molecule combines a basic residue (lysine, with a side-chain amine) and an acidic residue (glutamate, with a side-chain carboxylic acid), so it carries both positive and negative charges at neutral pH. PubChem’s computed XLogP of -6.3 indicates very high water solubility.

Key identifiers

• CAS number: 45234-02-4
• InChIKey: UGTZHPSKYRIGRJ-YUMQZZPRSA-N
• UNII: H34V7IM5ML
• Synonyms: Lys-Glu, KE dipeptide, lysylglutamic acid, L-lysyl-L-glutamic acid, AB-0 peptide

The order of residues matters. Vilon is Lys-Glu; the reverse dipeptide, Glu-Lys, is a different compound with different identifiers. The Lys-Glu motif also occurs inside many larger proteins, but the name vilon refers only to the free, isolated dipeptide.

Research History and Development

Vilon research dates to around 2000, when Russian gerontology groups tested it for effects on tumors, lifespan and immune organs in rodents.

A 2000 report in Doklady Biological Sciences stated in its title that vilon inhibited growth of spontaneous tumors and increased the lifespan of mice.^[2] In 2001, an immunohistochemical study in rats examined its effects on radiosensitive organs.^[4] A 2002 DNA-microarray study then compared gene expression changes in mouse heart after vilon and epitalon treatment.^[3]

Work in the mid-2000s extended to chromatin activity in blood cells from people aged 75 to 88, and to interleukin-2 in the rat hypothalamus.^[5][6] A 2013 review by the developing group summarized long-term clinical studies of several peptide bioregulators, including vilon, as geroprotectors.^[7] A 2014 review proposed a role for vilon and epitalon in regulating the aging-related genes CCL11 and HMGB1.^[1]

Mechanisms Studied in Research

Proposed mechanisms for vilon center on gene regulation, including chromatin decondensation and changes in gene expression, along with effects on immune cell differentiation. These mechanisms are based on cell-culture and animal data.

Chromatin and gene expression

In blood leukocytes from subjects aged 75 to 88, vilon and four other short peptides activated ribosomal genes, decondensed tightly packed chromatin and released genes repressed by age-related condensation of euchromatin. Unlike epitalon, livagen and prostamax, vilon was not reported to decondense the pericentromeric heterochromatin of chromosome 1.^[5] In mouse heart tissue, vilon alone changed expression of 36 of 15,247 clones by more than twofold, compared with 98 for epitalon and 144 for the combination. Vilon alone or combined with epitalon activated 157 clones, by up to 6.13-fold, and inhibited 23, which the authors described as a peptide-specific pattern.^[3]

Aging-related cytokine genes

A 2014 review proposed that vilon and epitalon act on the genes for CCL11 (eotaxin) and HMGB1, cytokines described as molecular markers of aging, and suggested that their geroprotective action may involve suppression of these genes.^[1]

Immune cell differentiation

In cultured human and rat thymus cells, vilon (coded AB-O) and an analogue (R-1) both increased expression of the lymphocyte differentiation marker CD5. Vilon steered T-cell precursors toward CD4+ helper cells, but its effect was weaker than that of the analogue.^[8]

Oxidative balance

In vitro, vilon and related short peptides showed no direct antioxidant activity but limited lipid peroxidation of human lipoproteins by modifying their structure, increased red blood cell membrane stability against osmotic hemolysis and reduced the percentage of dead cells in neuronal cultures, even though intracellular reactive oxygen species levels rose. The authors suggested that short peptides may take part in regulating apoptosis and necrosis.^[9]

Key Findings From Published Studies

Published vilon findings come mostly from rodent and cell-culture studies by a single research network, with clinical results available only through review articles.

Animal studies

• Radiation recovery: in rats exposed to a single whole-body gamma irradiation, vilon stimulated thymocyte proliferation and enhanced the proliferative potential of intestinal stem cells, which the authors interpreted as faster post-radiation recovery of critical organs. In the same study, epitalon had a different profile, slowing metabolic processes in the duodenal mucosa and suppressing blood cell formation in the spleen.^[4]
• Transplanted tumors: in mice with transplanted Lewis lung carcinoma, vilon alone significantly increased survival, but giving it at the same time as cyclophosphamide decreased survival. The authors concluded the two should not be used synchronously.^[10]
• Spontaneous tumors and lifespan: an early report described inhibited spontaneous tumor growth and increased lifespan in mice.^[2]
• Breast tumors in transgenic mice: in HER-2/neu transgenic mice treated with vilon or epitalon, the abstract reports tumor inhibition and reduced HER-2/neu expression for epitalon only, without a comparable result for vilon.^[11]
• Hypothalamic interleukin-2: in rats under mild handling stress, vilon and epitalon changed the number of IL-2-containing cells in hypothalamic structures. IL-2-positive cells decreased within 2 hours after intranasal delivery of the test peptides.^[6]

In-vitro studies

• In spleen tissue explants from 1-day-old and 2-year-old rats, vilon stimulated apoptosis and abolished the inhibitory effect of cyclophosphamide on explant growth.^[10]
• In elderly subjects’ leukocytes, vilon activated ribosomal genes and decondensed facultative heterochromatin.^[5]

Human evidence

Clinical use of vilon is described in a 2013 review of the developing group’s long-term studies, but the indexed abstract gives no trial design, sample sizes or outcomes.^[7] Independent controlled trials are not represented in the literature reviewed here.

Because vilon and its reverse dipeptide share a formula, researchers typically confirm sequence identity with HPLC and mass spectrometry certificates of analysis.

Regulatory and Research Status

Vilon 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 appears in the literature as an investigational dipeptide.

Nearly all published vilon studies come from Russian research groups connected to the institute where it was created, and several key reports are available only as titles or brief abstracts in English.^[2][7] Independent replication is limited.

The interaction with cyclophosphamide in the Lewis lung carcinoma model, where simultaneous treatment reduced survival, is one of the few published signals relevant to safety and combination research.^[10] Further controlled studies would be needed to establish how the rodent and cell findings relate to human biology.