Key findings
- In cerebellar granule cells, neutrophils and PC12 cells under oxidative stress the peptide limited reactive oxygen species accumulation in a concentration dependent way and lowered necrotic cell death measured by propidium iodide. [1]
- Fluorescence quenching constants for labelled deoxyribooligonucleotides differed by peptide primary structure, and the authors report the tripeptide binding preferentially to CNG containing and CAG containing sequences while discriminating cytosine methylation status. [2]
- Spectral, NMR, viscosimetry and molecular dynamics work places the tripeptide partly inside the DNA major groove in contact with the N7 and O6 atoms of guanine, with magnesium ions promoting the interaction by screening phosphate charge. [3]
- In induced cortical neurons transdifferentiated from dermal fibroblasts of elderly donors the tripeptide increased the number of primary processes and the total dendrite length and lowered oxidative DNA damage, while leaving mitochondrial and lysosomal activity and p16 protein unchanged. [4]
Identity and structure
- Family
- One of a set of short regulatory peptides studied together with Ala-Glu-Asp-Gly, Lys-Glu-Asp-Gly and Ala-Glu-Asp-Leu in the same nucleic acid binding work [2]
- Form as supplied
- Sterile lyophilized powder
Mechanism as studied
Two separable activities are reported in the same cell study. Limiting reactive oxygen species accumulation and cell mortality saturated at lower concentrations while modification of the cell cycle continued at higher ones, which the authors read as an antioxidant activity plus a direct interaction with the cell genome. [1]
The genome interaction is described at the level of sequence recognition rather than of a receptor. Labelled tripeptide entered the cytoplasm, nucleus and nucleolus of HeLa cells, and quenching constants against single-stranded and double-stranded oligonucleotides show binding that distinguishes nucleotide sequences and cytosine methylation state. [2]
Molecular dynamics and NMR add a geometry for that binding. The tripeptide partly enters the major groove and contacts guanine base atoms, and divalent magnesium promotes the contact by screening the negatively charged phosphate backbone, an effect that persists in salted solution. [3]
Research findings
In vitro
- System
- Rat cerebellar granule cells, neutrophils and pheochromocytoma PC12 cells under oxidative stress driven by receptor dependent and receptor independent stimuli
- Measured
- Reactive oxygen species accumulation across a concentration range, necrotic cell death by propidium iodide, the time course of ERK 1/2 activation and cell cycle distribution
- Reported
- Reactive oxygen species accumulation was restricted in a concentration dependent way and necrotic death fell. ERK 1/2 activation showed a delayed time course and the cell cycle was modified. Because the radical and mortality effects saturated at lower concentrations than the cell cycle effect, the authors infer a second activity beyond antioxidant action. [1]
In vitro
- System
- HeLa cells incubated with fluorescein isothiocyanate labelled peptides, so the cell penetration part used a labelled analogue rather than the unmodified tripeptide, alongside epithalon and testagen
- Measured
- Fluorescence in cytoplasm, nucleus and nucleolus, and Stern-Volmer quenching constants for carboxyfluorescein labelled single-stranded and double-stranded deoxyribooligonucleotides and for DNA ethidium bromide complexes
- Reported
- Labelled peptide fluorescence appeared in cytoplasm, nucleus and nucleolus. Quenching constants differed by peptide primary structure, indicating specific interaction with nucleic acid structures that discriminates nucleotide sequence and cytosine methylation status, with preferential binding to CNG and CAG containing sequences for this tripeptide. [2]
Structural
- System
- DNA in solution studied with the unmodified tripeptide, in the absence and presence of monovalent and divalent ions
- Measured
- Spectral, NMR and viscosimetry observables plus molecular dynamics trajectories describing the site and depth of the interaction
- Reported
- The tripeptide partly penetrated the major groove and affected base atoms, mainly N7 and O6 of guanine. Magnesium ions promoted the interaction by screening the negatively charged phosphate groups, and that promotion persisted in salted solution. [3]
In vitro
- System
- Induced cortical neurons transdifferentiated from dermal fibroblasts of elderly donors, with Lys-Glu-Asp and Ala-Glu-Asp-Gly tested alongside this tripeptide rather than this tripeptide alone
- Measured
- Number of primary dendritic processes and total dendrite length, mitochondrial and lysosomal activity, p16 and LaminB1 protein levels and oxidative DNA damage
- Reported
- All three peptides increased the number of primary processes and the total length of dendrites. None of them changed mitochondrial or lysosomal activity or p16 level. This tripeptide specifically lowered oxidative DNA damage in the induced neurons. [4]
Preclinical in vivo
- System
- Offspring of rats given a dietary methionine load during pregnancy to produce experimental hyperhomocysteinemia, with cerebellar neurons isolated from the offspring for the cellular measurements
- Measured
- Spatial orientation and learning in the offspring, and reactive oxygen species accumulation and necrotic cell counts in the isolated cerebellar neuron population
- Reported
- Offspring of the peptide exposed dams showed better spatial orientation and learning, and their isolated cerebellar neurons accumulated less reactive oxygen species and contained fewer necrotic cells than offspring of the methionine loaded control dams. [5]
Preclinical in vivo
- System
- 5xFAD and 5xFAD-M mouse models, with the Lys-Glu-Asp peptide tested in parallel, plus an in silico docking arm using double-stranded DNA covering all hexanucleotide combinations
- Measured
- Dendritic spine density and morphology, neuroplasticity readouts, and the lowest energy docking complexes of each peptide with B-form DNA
- Reported
- Both peptides prevented dendritic spine loss in the 5xFAD-M mice. Docking placed binding sites for this tripeptide in the promoter regions of CASP3, NES, GAP43, APOE, SOD2, PPARA, PPARG and GDX1, which the authors present as a proposed epigenetic route rather than a measured one. [6]
Handling for in-vitro work
- Labelling in cited work
- Cell penetration was followed with a fluorescein isothiocyanate conjugate; the DNA interaction work used the unlabelled tripeptide [2][3]
- Assay condition in cited work
- Divalent magnesium in the buffer promoted the DNA interaction and its effect persisted in salted solution [3]
- Storage
- Lyophilized at -20 °C, dark and dry; reconstituted aliquots kept cold and used promptly
Open questions
- The cited work does not identify a receptor or transporter that carries the tripeptide across the plasma membrane; entry was inferred from a labelled conjugate.
- Sequence preference is reported from fluorescence quenching constants and docking energies rather than from a solved peptide DNA structure.
- Whether the promoter binding sites found by docking correspond to measured transcript changes is not established in the cited studies.
- Several of the cited studies test this tripeptide alongside related short peptides, so effects specific to this sequence are separable only where the authors report them separately.
A clinical literature on short regulatory peptides exists and concerns finished formulations; it is out of scope for a research material profile.
Lot records
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Read a certificate of analysis ↗References
- Khavinson V, Ribakova Y, Kulebiakin K, et al. Pinealon increases cell viability by suppression of free radical levels and activating proliferative processes. Rejuvenation research. 2011.
- Fedoreyeva LI, Kireev II, Khavinson VKh, et al. Penetration of short fluorescence-labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNA. Biochemistry. Biokhimiia. 2011.
- Silanteva IA, Komolkin AV, Morozova EA, et al. Role of Mono- and Divalent Ions in Peptide Glu-Asp-Arg-DNA Interaction. The journal of physical chemistry. B. 2019.
- Kraskovskaya N, Linkova N, Sakhenberg E, et al. Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related Changes. International journal of molecular sciences. 2024.
- Arutjunyan A, Kozina L, Stvolinskiy S, et al. Pinealon protects the rat offspring from prenatal hyperhomocysteinemia. International journal of clinical and experimental medicine. 2012.
- Khavinson V, Ilina A, Kraskovskaya N, et al. Neuroprotective Effects of Tripeptides-Epigenetic Regulators in Mouse Model of Alzheimer's Disease. Pharmaceuticals (Basel, Switzerland). 2021.
Publication records fetched from PubMed on 2026-09-20. Profile text reviewed 2026-09-20.