Cortagen

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.

Molecular Profile

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

Mechanism & Target Class

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.

Storage & Handling

Lyophilized
−20 °C, protected from light and moisture; documented in the originating patent as a white amorphous odorless powder.
Handling
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.

Primary Database

PubChem CID 11690869 ↗

References (22)

  1. Reviews

    1

    Khavinson VK, Popovich IG, Linkova NS, Mironova ES, Ilina AR (2021). Molecules

    DOI: 10.3390/molecules26227053PubMed 34834147

  2. 2

    Khavinson VK, Lin'kova NS, Tarnovskaya SI, et al. (2016). Bulletin of Experimental Biology and Medicine

    DOI: 10.1007/s10517-016-3596-7

  3. 3

    Vanyushin BF, Khavinson VK (2016). Epigenetics – A Different Way of Looking at Genetics (Springer)

    DOI: 10.1007/978-3-319-27186-6_5

  4. Primary research

    4

    Lazareva EM, Kazakov EP, Dilovarova TA, Kononenko NV, Fedoreyeva LI (2025). International Journal of Molecular Sciences

    DOI: 10.3390/ijms262211028PubMed 41303518

  5. 5

    Fedoreyeva LI, Vanyushin BF, Baranova EN (2020). AIMS Biophysics

    DOI: 10.3934/biophy.2020001

  6. 6

    Morozova EA, Lin'kova NS, Khavinson VK, Soloviev AY, Kasyanenko NA (2017). Journal of Structural Chemistry

    DOI: 10.1134/S0022476617020299

  7. 7

    Fedoreyeva LI, Dilovarova TA, Ashapkin VV, et al. (2017). Biochemistry (Moscow)

    DOI: 10.1134/S0006297917040149

  8. 8

    Kuzubova NA, Lebedeva ES, Dvorakovskaya IV, et al. (2015). Bulletin of Experimental Biology and Medicine

    DOI: 10.1007/s10517-015-3047-xPubMed 26468022

  9. 9

    Khavinson VK, Tendler SM, Vanyushin BF, et al. (2014). Lung

    DOI: 10.1007/s00408-014-9620-7PubMed 25015171

  10. 10

    Khavinson VK, Linkova NS, Polyakova VO, et al. (2012). Bulletin of Experimental Biology and Medicine

    DOI: 10.1007/s10517-012-1664-1PubMed 22808515

  11. 11

    Fedoreyeva LI, Kireev II, Khavinson VK, Vanyushin BF (2011). Biochemistry (Moscow)

    DOI: 10.1134/S0006297911110022PubMed 22117547

  12. 12

    Monaselidze JR, Khavinson VK, Gorgoshidze MZ, et al. (2011). Bulletin of Experimental Biology and Medicine

    DOI: 10.1007/s10517-011-1146-xPubMed 21240358

  13. 13

    Khavinson VK, Ryzhak GA, et al. (2009). US Patent 7,625,870

    Source

  14. 14

    Khavinson VK (2001). Bulletin of Experimental Biology and Medicine

    DOI: 10.1023/A:1013058701974PubMed 11713572

  15. 15

    Turchaninova LN, Kolosova LI, Malinin VV, Moiseeva AB, Nozdrachev AD, Khavinson VK (2000). Bulletin of Experimental Biology and Medicine

    DOI: 10.1023/A:1017532001908PubMed 11276314

  16. 16

    Anisimov SV, Boheler KR, Khavinson VK, Anisimov VN (2004). Neuro Endocrinology Letters

    PubMed 15159690

  17. 17

    Zarubina IV, Shabanov PD (2011). Eksperimental'naia i Klinicheskaia Farmakologiia

    PubMed 21476278

  18. 18

    Shabanov PD, Vislobokov AI (2013). Reviews on Clinical Pharmacology and Drug Therapy

    DOI: 10.17816/RCF11217-25

  19. 19

    Lezhava T, Monaselidze J, Jokhadze T, Buadze M, Gaiozishvili M (2015). International Journal of Peptide Research and Therapeutics

    DOI: 10.1007/s10989-014-9443-7

  20. 20

    Lezhava T, Jokhadze T, Monaselidze J, Buadze T, Gaiozishvili M, Sigua T (2020). Georgian Medical News

    PubMed 33526740

  21. 21

    Khavinson VK, Lin'kova NS, Tarnovskaya SI, Umnov RS, Elashkina EV, Durnova AO (2014). Bulletin of Experimental Biology and Medicine

    DOI: 10.1007/s10517-014-2496-yPubMed 24909721

  22. 22

    Caputi S, Trubiani O, Sinjari B, Trofimova S, Diomede F, Linkova N, Diatlova A, Khavinson V (2019). International Journal of Immunopathology and Pharmacology

    DOI: 10.1177/2058738419828613PubMed 30791821