Ovagen Peptide

Hepatic tripeptide normalizing liver parenchymal cell function. Research shows improved lipid metabolism (reduced hepatic steatosis), enhanced albumin synthesis, and normalized bilirubin conjugation in aging liver models.

Ovagen (Glu-Asp-Leu) is a short-chain peptide bioregulator developed at the St. Petersburg Institute of Bioregulation and Gerontology as part of the Khavinson family of cytogenes. Like other tripeptide bioregulators (Epitalon, Vilon, Pinealon, Livagen), Ovagen is hypothesized to act through direct interaction with DNA promoter regions, modulating gene expression in tissue-specific patterns. In preclinical research, Ovagen has been characterized as a hepatotropic and immunotropic regulator with reported effects on hepatocyte proliferation, lipid metabolism, and lymphocyte function.

Epigenetic and Gene Expression Modulation

Khavinson and colleagues have proposed that small peptides such as Glu-Asp-Leu penetrate the cell membrane and nuclear envelope, where they bind to specific nucleotide sequences in gene promoters. Molecular modeling studies suggest that Ovagen interacts preferentially with CpG-rich regions associated with hepatocyte differentiation genes. This binding is hypothesized to displace histone H1 and facilitate transcription factor access, leading to upregulation of genes involved in liver regeneration, including HNF-4α, albumin, and cytochrome P450 isoforms.

Hepatocyte Proliferation and Regeneration

In rodent models of hepatic injury (CCl₄-induced toxicity, partial hepatectomy), Ovagen administration has been associated with accelerated mitotic activity in hepatocytes, normalization of serum transaminases (ALT, AST), and restoration of bilirubin clearance. The peptide appears to enhance the proliferative pool of hepatocytes without inducing hyperplasia, suggesting a regulatory rather than mitogenic mechanism.

Lipid Metabolism Regulation

Ovagen has been investigated for its effects on cholesterol and triglyceride metabolism. In aged animal models, the tripeptide has been associated with reductions in total cholesterol, LDL, and hepatic steatosis markers. Proposed mechanisms include modulation of SREBP-1c expression and upregulation of LDL receptor synthesis in hepatocytes.

Immunomodulatory Effects

Beyond hepatic action, Ovagen has been characterized as an immunoregulator. Research suggests it influences T-lymphocyte differentiation and natural killer (NK) cell activity, possibly through regulation of interleukin gene expression. This dual hepatic-immune action distinguishes Ovagen from purely hepatotropic agents and aligns it with the broader Khavinson concept of peptide bioregulation, in which short peptides serve as endogenous signaling molecules between tissue compartments.

Comparison to Related Bioregulators

Ovagen is structurally distinct from Livagen (Lys-Glu-Asp), another hepatic bioregulator, despite overlapping research applications. While Livagen has been more extensively studied for chromatin decondensation in lymphocytes, Ovagen research has focused predominantly on hepatocyte function and lipid handling. Both peptides share the Khavinson hypothesis of sequence-specific DNA interaction as the unifying mechanism.

Importantly, the precise molecular targets of Ovagen remain under active investigation, and most mechanistic data derive from Russian-language preclinical literature. Western validation through receptor binding studies and chromatin immunoprecipitation assays is limited, and Ovagen is currently classified as a research compound only.

Ovagen is a synthetic tripeptide composed of glutamic acid, aspartic acid, and leucine. The compound's physicochemical properties reflect its short-chain structure and predominantly anionic character at physiological pH, due to two free carboxyl side chains.

Structural Notes

The Glu-Asp-Leu sequence presents an acidic N-terminal dipeptide followed by a hydrophobic leucine residue. This amphipathic character is thought to facilitate both aqueous transport and membrane permeation, consistent with the Khavinson model of peptide bioregulator pharmacokinetics. The absence of cysteine residues means Ovagen lacks disulfide bond stabilization, but also confers stability against oxidative degradation that affects sulfur-containing peptides.

The peptide is achiral-free at the alpha-carbon level (all L-amino acids) and does not contain any non-canonical residues, modifications, or cyclization. Synthesis is typically performed via solid-phase Fmoc chemistry with subsequent HPLC purification. Mass spectrometry confirmation (expected [M+H]⁺ = 376.18) and HPLC purity assessment are standard quality control measures.

Ovagen (Glu-Asp-Leu) is supplied as a sterile lyophilized powder. The tripeptide is relatively stable compared to larger peptides but still benefits from careful handling to preserve research-grade integrity. The following protocol is provided for laboratory research use only.

Reconstitution Protocol

1. Allow the vial to equilibrate to room temperature for 15-20 minutes after removal from -20°C storage. This prevents condensation from forming inside the vial when the stopper is pierced.
2. Select an appropriate solvent. Bacteriostatic water (0.9% benzyl alcohol) or sterile water for injection are standard choices for short peptides. Ovagen's three charged/polar side chains (two carboxylates from Glu and Asp, plus the N- and C-termini) confer good aqueous solubility.
3. Calculate target concentration. A common working solution is 5 mg peptide in 1 mL solvent, yielding 5 mg/mL. For a 10 mg vial, adding 2 mL of solvent produces the same concentration.
4. Inject solvent slowly down the inner wall of the vial rather than directly onto the lyophilized powder. This minimizes mechanical disruption.
5. Allow the powder to dissolve passively over 2-3 minutes. Gentle swirling can assist dissolution.
6. Do NOT vortex or shake vigorously. Although Ovagen lacks disulfide bonds, mechanical agitation can introduce air, increase surface area for oxidation, and cause minor losses.
7. Inspect the solution — properly reconstituted Ovagen should be clear and colorless with no particulates.

Compound-Specific Notes

• pH sensitivity: Ovagen's two acidic residues mean the solution will be mildly acidic (~pH 4-5) in pure water. Buffering with PBS may be preferable for in vitro applications requiring physiological pH.
• No methionine or cysteine — Ovagen is not subject to oxidative degradation pathways that affect Met- or Cys-containing peptides, simplifying handling.
• Low molecular weight (375 Da): The tripeptide may pass through some dialysis membranes designed for larger molecules; verify membrane MWCO before use in purification workflows.
• Aliquot for repeated use. Divide reconstituted stock into single-use aliquots (e.g., 100 µL) to avoid repeated freeze-thaw cycles, which can degrade short peptides over time.

All handling should be performed in a clean laminar flow environment using sterile technique. AminoCore Research products are intended solely for in vitro research and laboratory investigation by qualified personnel.

Proper storage of Ovagen (Glu-Asp-Leu) is essential to maintain peptide integrity and research reproducibility. Short tripeptides are generally more stable than larger peptides, but appropriate temperature control and protection from moisture remain critical.

Lyophilized Powder Storage

• Long-term (≥1 month): Store at -20°C in the original sealed vial. Under these conditions, Ovagen lyophilized powder maintains stability for 24+ months from the date of manufacture.
• Short-term (≤30 days): Storage at 2-8°C (standard refrigeration) is acceptable for active research use.
• Transit/room temperature: Lyophilized Ovagen tolerates short-term exposure to ambient temperatures (up to 7-10 days) without measurable degradation due to the absence of labile residues.
• Protect from moisture: Keep the desiccant pouch (if included) in proximity to the vial. Atmospheric humidity can cause the lyophilized cake to absorb water and degrade.

Reconstituted Solution Storage

• 2-8°C (refrigerated): Reconstituted Ovagen in sterile aqueous solution is typically stable for 14-21 days when stored sealed and protected from light.
• -20°C (frozen aliquots): Single-use aliquots can be stored for 3-6 months. Avoid repeated freeze-thaw cycles, which gradually reduce peptide concentration through aggregation and adsorption to vial walls.
• Room temperature: Not recommended for reconstituted solutions beyond the duration of an experimental session.

Compound-Specific Stability Considerations

• No disulfide bonds: Unlike cysteine-containing peptides, Ovagen is not subject to oxidative crosslinking or scrambling.
• No methionine: No risk of oxidation to methionine sulfoxide that could alter activity.
• Acidic residue susceptibility: The Glu and Asp residues can undergo isomerization (succinimide formation, particularly at Asp) under prolonged storage at neutral-to-alkaline pH. Acidic storage conditions minimize this risk.
• Light exposure: While Ovagen lacks aromatic residues (no Trp, Tyr, Phe), good laboratory practice includes storing peptide solutions protected from direct light.

Always document the reconstitution date on the vial label and discard solutions that show cloudiness, color change, or particulate formation. AminoCore Research provides a Certificate of Analysis with each lot, listing recommended storage conditions and expiration dating based on stability testing.