Epitalon — also spelled Epithalon or Epithalone, and sometimes written by its sequence, AEDG — is one of the smallest peptides in the longevity-research literature and one of the easiest to characterize. This note covers the molecule itself, how it is made and purified, what a correct certificate of analysis for it looks like, and what the published laboratory work has and has not examined.
The molecule
| Sequence | H-Ala-Glu-Asp-Gly-OH (AEDG) |
|---|---|
| Formula | C14H22N4O9 |
| Monoisotopic mass | 390.14 Da (average 390.35 g/mol) |
| CAS | 307297-39-8 |
| Charge at neutral pH | Net −2 (two side-chain carboxyls plus the C-terminus, one N-terminal amine) |
| Character | Small, hydrophilic, acidic; freely water-soluble; no chromophore beyond the peptide bond, so UV detection at 214–220 nm |
AEDG was designed at the St. Petersburg Institute of Bioregulation and Gerontology by Vladimir Khavinson’s group as a synthetic stand-in for epithalamin, a polypeptide extract of bovine pineal gland that had been studied in the Soviet Union since the 1970s. The four-residue sequence was chosen from the amino-acid composition of the extract rather than from a defined parent protein, which is why AEDG has no natural “source” in the way that thymosin β4 or GHK do.
Synthesis and purification
Epitalon is made by standard solid-phase peptide synthesis (Fmoc chemistry on a Wang or 2-chlorotrityl resin), which for a four-residue sequence is a routine, high-yield process. The only synthetic subtlety is the Asp-Gly bond: aspartate followed by glycine is the classic sequence for aspartimide formation during Fmoc deprotection, which produces a cyclic imide side product with the same mass as the parent peptide. Good synthesis protocols use a protected Asp derivative or additives to suppress it. Because the impurity is isobaric, mass spectrometry will not reveal it; only HPLC will, as a separate peak with a slightly different retention time.
After cleavage from the resin the crude product is purified by preparative reverse-phase HPLC and lyophilized. The counter-ion is trifluoroacetate unless the supplier performs a salt exchange to acetate; the salt form affects the net peptide content of the vial (an acetate salt of AEDG is about 87% peptide by mass) and should be stated on the COA.
What a correct COA looks like
On reverse-phase HPLC with a water/acetonitrile gradient at 214 nm, AEDG elutes early — it is very hydrophilic — as a single sharp peak. Purity in the high nineties is achievable and typical for a peptide this short. On electrospray MS the expected ions are [M+H]+ at m/z 391.1 and [M+Na]+ at 413.1; in negative mode, [M−H]− at 389.1. Any of these, matching within instrument tolerance, confirms identity. A certificate that shows an HPLC trace but no mass spectrum has not confirmed that the peak is AEDG.
Stability
AEDG has no oxidation-sensitive residues, so its stability problems are hydrolytic. The Asp-Gly bond is the weak point: in aqueous solution, especially at low pH, it is prone to cleavage and to the same aspartimide rearrangement that complicates synthesis. As a dry lyophilizate at −20 °C the peptide is stable for years; in solution it should be used within days if refrigerated, or frozen in single-use aliquots.
What the laboratory literature has examined
The published work on AEDG comes largely from the Khavinson group and collaborators and falls into three areas. First, telomerase activity and telomere length in cultured human somatic cells — the 2003 paper in the Bulletin of Experimental Biology and Medicine is the most-cited. Second, aged-animal models (rats, mice, Drosophila) in which circadian, neuroendocrine and lifespan endpoints were measured. Third, more recent molecular work on the peptide’s binding to DNA and histone proteins and its effects on gene expression (for example CD5, IL-2, MMP-2) in cell lines.
Two caveats apply to all of it. Most of the studies come from a single research programme with limited independent replication, and none of the findings has been tested in a controlled human trial. They are laboratory results in cells and animals and should be read as such.
Alpha Forge Prime supplies synthetic peptides for in-vitro laboratory research only. Nothing on this page describes or recommends any use in humans or animals. Products are not drugs and have not been evaluated by the FDA.
