Signaling
A synthetic tetrapeptide (Ala-Glu-Asp-Leu) studied in non-clinical models as a short-peptide bioregulator of gene expression in bronchopulmonary and related cell systems.
Cortagen is a short, synthetic four-amino-acid peptide (sequence Ala-Glu-Asp-Leu, abbreviated AEDL) belonging to the Khavinson class of peptide bioregulators. It is studied in laboratory models of bronchial and pulmonary tissue, where investigators examine its interaction with DNA and chromatin and its association with tissue-specific gene-expression patterns.
Type
Synthetic linear tetrapeptide
Molecular formula
C18H30N4O9
Molecular weight
446.45 g/mol
Amino acids
4
Sequence
Ala-Glu-Asp-Leu
Modification
Unmodified free N-/C-termini; documented in the originating patent as an acetate salt
Cortagen belongs to the Khavinson class of short regulatory peptides — sequences of 2–7 amino acid residues proposed to act as epigenetic modulators by penetrating cell nuclei and interacting directly with DNA and histone proteins rather than through classical receptor engagement. In vitro biophysical characterization (Morozova et al., 2017) using UV spectrophotometry, circular dichroism, and viscometry reports that AEDL forms a complex with double-stranded DNA at the guanine N7 position in the major groove without visible distortion of the double-helix structure. Differential scanning microcalorimetry work (Monaselidze et al., 2011) documents a DNA-thermostabilizing interaction with calf thymus and mouse liver DNA across a defined molar-ratio range, characterized as non-sequence-specific. Docking-based spatial modeling (Khavinson, Lin'kova & Tarnovskaya, 2016) assigns the AEDL and EDL sequences to a CTCC tetranucleotide binding motif at gene-promoter sites. Histone-binding experiments (Fedoreyeva, Vanyushin & Baranova, 2020) report AEDL interaction with linker histone H1 and core histone H3 associated with remodeling of condensed-chromatin domains. At the transcript level, AEDL is studied in human bronchial epithelial cell cultures for association with expression of differentiation factors NKX2-1, SCGB1A1, SCGB3A2, FOXA1, and FOXA2, mucin and surfactant genes MUC4, MUC5AC, and SFTPA1, and cell-cycle and signaling proteins Ki67, Mcl-1, p53, CD79, and NOS-3.
Research Focus
Studied in non-clinical molecular-biology, biophysical, and preclinical models focused on peptide–DNA interaction, chromatin regulation, and tissue-specific gene-expression in bronchopulmonary and comparative cell systems.
Cortagen (Ala-Glu-Asp-Leu) is one of a family of synthetic short peptides developed within the Khavinson peptide-bioregulator research program at the St. Petersburg Institute of Bioregulation and Gerontology, which produced defined-sequence peptides by directed synthesis modeled on motifs identified in tissue peptide extracts. The AEDL sequence and its synthetic characterization — molecular formula C18H30N4O9; molecular weight 446.45 g/mol; documented as an acetate salt at approximately 98% HPLC peptide content — are recorded in US Patent 7,625,870 (Khavinson et al., 2009). The framework positing that short peptides of 2–7 residues may penetrate cells, enter the nucleus, and interact with DNA to associate with gene-expression changes is reviewed by Vanyushin & Khavinson (2016) and examined across the class in the systematic review by Khavinson et al. (2021). This literature originates overwhelmingly from a single research group and affiliated laboratories, and independent replication of the core DNA-interaction mechanism outside this group has not been identified.
The most sequence-specific applied work places Cortagen in bronchial and pulmonary cell and tissue models. Khavinson et al. (2014, Lung) characterized Ki67, Mcl-1, p53, CD79, and NOS-3 protein levels across serial passages of human embryonic bronchoepithelial cell cultures alongside expression profiling of bronchial-differentiation factors NKX2-1, SCGB1A1, SCGB3A2, FOXA1, and FOXA2 and mucin/surfactant genes MUC4, MUC5AC, and SFTPA1; the study also included spectrophotometric, viscometric, and circular-dichroism examination of the peptide–DNA interaction. Khavinson et al. (2012, Bulletin of Experimental Biology and Medicine) examined differentiation-factor transcripts including CXCL12 and Hoxa3 in serially passaged human bronchial epithelial cultures — used as an in vitro model of replicative senescence — applying the AEDL tetrapeptide as the tissue-matched peptide alongside non-matched short peptides as controls. In a rodent preclinical system, Kuzubova et al. (2015) used a 60-day intermittent nitrogen dioxide–exposure protocol in rats as a model of obstructive lung pathology and assessed bronchial-epithelial morphology endpoints — goblet-cell hyperplasia, squamous metaplasia, and ciliated-cell status — and secretory immunoglobulin A as a mucosal marker.
A separate strand of biophysical work characterizes AEDL–nucleic acid and AEDL–chromatin interactions in isolation. Monaselidze et al. (2011, Bulletin of Experimental Biology and Medicine) applied differential scanning microcalorimetry to measure DNA melting thermodynamics across a range of peptide-to-DNA base-pair molar ratios, examining interactions with calf thymus and mouse liver DNA. Morozova et al. (2017, Journal of Structural Chemistry) employed UV spectrophotometry, circular dichroism, and viscometry to characterize complex formation in solution at varying ionic strength and reported binding at the guanine N7 position in the major groove without visible duplex distortion. Fedoreyeva, Vanyushin & Baranova (2020, AIMS Biophysics) examined chromatin-conformation changes associated with AEDL exposure, reporting binding to linker histone H1 and core histone H3 and associated remodeling of condensed-chromatin domains. Nuclear penetration of fluorescently labeled short peptides in the Khavinson class was examined in HeLa cell cultures by Fedoreyeva et al. (2011, Biochemistry (Moscow)) as a mechanistic entry point for the proposed nucleus-targeting model. Docking-based modeling (Khavinson, Lin'kova & Tarnovskaya, 2016) associates the AEDL and EDL sequences with a CTCC promoter tetranucleotide binding site.
The proposed DNA-interaction mechanism has been examined in plant model systems as part of a broader argument for cross-kingdom conservation. Lazareva et al. (2025, International Journal of Molecular Sciences) characterized metabolism and autophagy markers — including the autophagy marker ATG8, cytochrome c release, and TUNEL-detected DNA strand breaks — in root cells of Nicotiana tabacum exposed to the AEDL tetrapeptide. An earlier study by Fedoreyeva et al. (2017, Biochemistry (Moscow)) examined AEDL alongside related short peptides for associations with expression of CLE, KNOX1, and GRF gene families in the same plant model system. These comparative studies are cited by the originating research group as supporting a conserved peptide–DNA interaction mechanism; they do not independently establish relevance in mammalian or human systems.
Lyophilized
−20 °C, protected from light and moisture
documented in the originating patent as a white amorphous odorless powder.
Reconstituted
2–8 °C for short-term use
avoid repeated freeze–thaw cycles.
As an unprotected tetrapeptide composed of common L-amino acids, AEDL would be expected to be susceptible to proteolytic degradation; no formal pharmacokinetic study measuring the intact peptide was identified in the verified literature.
Reviews
Khavinson VK, Popovich IG, Linkova NS, Mironova ES, Ilina AR (2021). Molecules — Systematic review — peptide regulation of gene expression across the Khavinson short-peptide class
Khavinson VK, Lin'kova NS, Tarnovskaya SI, et al. (2016). Bulletin of Experimental Biology and Medicine — Methods/modeling review — docking models of short cell-penetrating peptides at gene-promoter sites
Vanyushin BF, Khavinson VK (2016). Epigenetics – A Different Way of Looking at Genetics (Springer) — Book-chapter review — short peptides as epigenetic modulators of gene activity
Primary research
Lazareva EM, Kazakov EP, Dilovarova TA, Kononenko NV, Fedoreyeva LI (2025). International Journal of Molecular Sciences — Primary plant-cell study — AEDL tetrapeptide effects on metabolism and autophagy markers in Nicotiana tabacum root cells
Fedoreyeva LI, Vanyushin BF, Baranova EN (2020). AIMS Biophysics — Primary biophysical study — AEDL tetrapeptide chromatin-conformation change via histone H1/H3 binding
Morozova EA, Lin'kova NS, Khavinson VK, Soloviev AY, Kasyanenko NA (2017). Journal of Structural Chemistry — Primary in vitro biophysical study — AEDL tetrapeptide–DNA interaction in solution by spectrophotometry, CD, and viscometry
Fedoreyeva LI, Dilovarova TA, Ashapkin VV, et al. (2017). Biochemistry (Moscow) — Primary plant-gene-expression study — AEDL and related short peptides in CLE/KNOX1/GRF gene regulation in Nicotiana tabacum
Kuzubova NA, Lebedeva ES, Dvorakovskaya IV, et al. (2015). Bulletin of Experimental Biology and Medicine — Primary preclinical study — AEDL tetrapeptide in a rat nitrogen dioxide obstructive-lung model, bronchial-epithelium morphology and secretory-IgA endpoints
Khavinson VK, Tendler SM, Vanyushin BF, et al. (2014). Lung — Primary in vitro study — AEDL tetrapeptide gene expression and protein synthesis in human bronchial epithelium
Khavinson VK, Linkova NS, Polyakova VO, et al. (2012). Bulletin of Experimental Biology and Medicine — Primary in vitro study — tissue-specific differentiation-factor expression in serially passaged bronchial epithelial cultures
Fedoreyeva LI, Kireev II, Khavinson VK, Vanyushin BF (2011). Biochemistry (Moscow) — Primary in vitro study — nuclear penetration of Khavinson-class short peptides in HeLa cells
Monaselidze JR, Khavinson VK, Gorgoshidze MZ, et al. (2011). Bulletin of Experimental Biology and Medicine — Primary biophysical study — AEDL tetrapeptide effect on DNA thermostability by differential scanning microcalorimetry
Khavinson VK, Ryzhak GA, et al. (2009). US Patent 7,625,870 — Patent — synthesis and characterization of the Ala-Glu-Asp-Leu tetrapeptide for respiratory-organ research
Research Use Only
These products are intended for research purposes only and are not for human consumption. Not FDA approved. Not intended to diagnose, treat, cure, or prevent any disease.
