Vesugen—also written Vezugen and standardized here as KED for its sequence Lys–Glu–Asp—is a synthetic tripeptide “bioregulator” studied for vascular endothelium and neuroplasticity outcomes in preclinical models. It appears to act via epigenetic regulation of gene expression (DNA/histone interactions) with downstream effects reported for endothelin‑1 (EDN1), connexins (e.g., GJA1/Cx43), and SIRT1 in vascular cells, and markers of neurogenesis/synaptic plasticity in neuronal models. (Khavinson)

Fast Answer / Executive Summary (40–60 words)

Vesugen (KED) is a research‑only tripeptide (Lys–Glu–Asp) investigated as a vascular and neuroprotective “bioregulator.” Early work suggests KED can normalize endothelin‑1, restore connexins, and increase SIRT1 in endothelial cells, and support dendritic structure/neurogenesis markers in neuronal models—likely via short‑peptide interactions with DNA/histones that modulate gene expression. Human evidence remains limited. (PubMed)

Entity Properties (for researchers)

Property Details
Aliases / Synonyms Vesugen, Vezugen (transliteration), KED, Lys–Glu–Asp; lysyl‑glutamyl‑aspartic acid
Family / Pathway Short tripeptide “bioregulator”; vascular endothelium focus; epigenetic gene regulation via DNA/histone interactions; reported effects on EDN1, GJA1/Cx43, SIRT1, MKI67 (Ki‑67) promoter docking. (PubMed)
Sequence (AA) H‑Lys‑Glu‑Asp‑OH (K‑E‑D)
Molecular Weight (Da) ~390.39 (calculated average mass from residue masses + H₂O). (Vanderbilt University)
Molecular Formula C₁₅H₂₆N₄O₈ (PubChem entry: lysyl‑glutamyl‑aspartic acid). (PubChem)
CAS Not assigned (no widely recognized CAS for KED as of Oct 2025); PubChem CID: 87571363. (PubChem)
Typical Diluent(s) Sterile Water for Injection (SWFI); Bacteriostatic Water for Injection (BWFI) is sterile water with 0.9% benzyl alcohol for multi‑dose vial reconstitution (research settings). (DailyMed)
Example Concentrations (educational) 1–2 mg/mL in aqueous media (research laboratory preparation; adjust to assay). See stability/handling notes below. (General peptide stability evidence summarized in peer‑reviewed pharmaceutical literature.) (PMC)
Storage (lyophilized / after reconstitution) Lyophilized peptides are generally most stable at low temperature (≤ −20 °C) away from light/moisture; reconstituted solutions are less stable and typically stored cold for short periods—follow your lab’s validated stability program. (PMC)

Compliance note: This article is educational for researchers, not medical advice. No human use is endorsed or implied.

Core Concepts & Key Entities

What is Vesugen (KED) in simple terms?

Vesugen is a short, three‑amino‑acid peptide (Lys–Glu–Asp) studied as a tissue‑specific “bioregulator” for vascular endothelium and brain. It belongs to a family of ultrashort peptides investigated for epigenetic control of gene expression—by binding to DNA promoter motifs and/or histone proteins—to influence cell‑type‑specific functions. (Khavinson)

How might KED work mechanistically?

KED’s proposed mechanism is epigenetic modulation of gene transcription via direct interactions with DNA and nucleosomal histones, a behavior repeatedly documented for ultrashort peptides in vitro, in silico, and by biophysical methods. In endothelial models, KED normalized EDN1, restored connexins (e.g., Cx37/Cx40/Cx43), and increased SIRT1—changes tied to vasoprotective phenotypes. (MDPI)

A frequently cited table of peptide–DNA complementarity lists “Vesugen (KED) → GCCG” as a presumptive binding sequence in promoter regions, supporting the concept of sequence‑selective DNA interactions by tripeptides. (Khavinson)

What outcomes have been reported in vascular research?

In endothelial and vascular injury contexts, KED showed gene‑level changes consistent with improved microvascular homeostasis. Preclinical studies report EDN1 normalization, connexin re‑expression, and SIRT1 increases, which together suggest improved endothelial communication and anti‑senescence signaling. More independent replication is warranted. (PubMed)

What outcomes have been reported in neuronal/neuroplasticity research?

In Alzheimer’s disease (AD) models, KED preserved dendritic spines and improved dendritic tree metrics in vitro and in the 5xFAD mouse model, while modulating expression of neurogenesis and cell‑cycle genes (e.g., NES, GAP43, p16/p21). A 2024 study in induced neurons from older donors reported enhanced dendritic complexity with KED, with authors positing histone/nucleosome interactions as a likely regulatory route. (MDPI)

A succinct review on KED in AD‑related neurogenesis also notes regulation of SUMO1, APOE, and IGF1, aligning with broader literature on short‑peptide gene regulation. (PubMed)

What about clinical evidence?

Evidence in humans is limited and heterogeneous. A small Russian geriatric study suggested oral Pinealon + Vesugen improved cognitive/functional measures in workers exposed to harmful conditions, and a separate clinical report recommended these peptides as “geroprotectors.” These findings require larger, controlled replication and are not regulatory‑approved indications. (SpringerLink)

Step‑by‑Step / How‑To (Research Handling & Documentation)

Education‑only. Follow your institution’s SOPs, validated methods, and biosafety rules. The points below summarize common research practices supported by pharmaceutical stability guidance.

1) Plan your experiment and documentation

Define the assay (e.g., endothelial gene expression, neuronal morphology), pre‑register methods, and specify endpoints (e.g., EDN1 mRNA, Cx43 protein, dendritic length). Record lot numbers, storage conditions, and timelines to enable reproducibility. (General principles; see stability rationale below.) (PMC)

2) Confirm identity & properties

Log sequence (K‑E‑D), calculated MW (~390.39 Da), and reference PubChem CID 87571363 for chemical metadata in your ELN/LIMS to reduce ambiguity across suppliers. (Vanderbilt University)

3) Choose an appropriate diluent

For single‑use aliquots, Sterile Water for Injection is typical. For multi‑withdrawal research vials, BWFI (sterile water with 0.9% benzyl alcohol) is commonly used; note preservative cautions in neonatal/clinical contexts (relevant to safety training, not to endorse human use). (DailyMed)

4) Reconstitute under aseptic conditions

Warm the sealed vial to ambient before opening (to limit condensation), then reconstitute to a validated working concentration (e.g., 1–2 mg/mL) using sterile technique. Mix gently; avoid foaming. Document pH/vehicle and filter‑sterilize only if your method requires it. (Peptide stability guidance summarized below.) (PMC)

5) Aliquot and label immediately

Prepare single‑use aliquots to minimize freeze‑thaw. Label with peptide ID, lot, concentration, diluent, and expiry per your lab’s stability protocol. (Journal of Pharmaceutical Sciences)

6) Store appropriately (lyophilized vs. solution)

  • Lyophilized: Store desiccated, light‑protected, preferably ≤ −20 °C, per your QA plan.
  • In solution: Expect shorter stability; keep cold and adhere to pre‑set retest intervals. Use lyoprotectants if formulating and validate with forced‑degradation data when applicable. (PMC)

7) Thawing & handling

Thaw on ice or at 2–8 °C, swirl gently, and avoid repeated freeze–thaw. Discard if turbidity/precipitation or pH drift occurs beyond your acceptance criteria. (Royal Society Publishing)

Comparison / Alternatives (Where Does KED Fit?)

Answer in one line: KED (Vesugen) is vascular‑centric with cross‑over neuroplasticity signals, whereas EDR (Pinealon) and AEDG (Epitalon) are often positioned as neuro‑centric and genome/aging‑centric, respectively; all three are short peptides investigated for epigenetic regulation. (MDPI)

Important: These are research‑only peptides; comparative notes below summarize preclinical literature (not therapeutic recommendations).

Feature Vesugen (KED) Pinealon (EDR) Epitalon (AEDG)
Sequence / Type Lys–Glu–Asp (tripeptide) Glu–Asp–Arg (tripeptide) Ala–Glu–Asp–Gly (tetrapeptide)
Primary research focus Vascular endothelium; vasoprotective gene shifts; also neuroplasticity in AD models Neuroprotection/neurogenesis; dendritic spines; oxidative stress responses Chromatin/telomerase and wide gene‑regulatory effects in aging models
Mechanistic highlights DNA/histone interactions; EDN1 normalization, connexin restoration, SIRT1↑ DNA/histone interactions; preserves dendritic spines; supports dendritogenesis DNA binding; telomerase gene activation; chromatin decondensation in aging cells
Representative models Endothelial cultures; vascular injury/atherosclerosis; 5xFAD mice (neuro) Neuronal cultures; 5xFAD mice; induced neurons from aged donors Human fibroblasts; diverse cell lines; animal models
Selected gene markers EDN1, GJA1/Cx43, SIRT1; MKI67 promoter docking p16/p21, NES, GAP43; AD‑linked genes TERT/telomerase; broad genomic programs
Evidence type In vitro/in vivo (preclinical); mechanistic reviews In vitro/in vivo (preclinical); mechanistic reviews In vitro/in vivo; mechanistic and biophysical studies

Citations: KED vascular & SIRT1/connexins/EDN1; docking to MKI67 (Ki‑67) promoter; KED/EDR neuroplasticity; EDR/AEDG histone/DNA interactions; AEDG telomerase/chromatin. (PubMed)

Templates / Checklist / Example

Copy‑Ready Lab Checklist (KED Research Use Only)

  • Define objective: State your primary endpoint (e.g., EDN1 mRNA, Cx43, dendritic length).
  • Standardize identity: Record sequence (K‑E‑D), MW (~390.39 Da), PubChem CID 87571363. (Vanderbilt University)
  • Select diluent: SWFI for single‑use; BWFI (0.9% benzyl alcohol) for multi‑withdrawal research vials; document choice/rationale. (DailyMed)
  • Plan concentration: Pre‑specify a working concentration (e.g., 1–2 mg/mL) and assay volumes; validate solvent compatibility. (PMC)
  • Aseptic reconstitution: Warm vial to room temp before opening; reconstitute; mix gently; avoid foaming. (Royal Society Publishing)
  • Aliquot & label: Create single‑use aliquots; label with ID/lot/diluent/concentration/expiry per SOP. (Journal of Pharmaceutical Sciences)
  • Storage plan: Lyophilized ≤ −20 °C, desiccated, light‑protected; solutions short‑term cold; define retest intervals. (PMC)
  • Thawing SOP: Thaw on ice/2–8 °C; avoid repeat freeze–thaw. (Royal Society Publishing)
  • Assay controls: Include vehicle control, unrelated tripeptide control, and positive control if applicable.
  • Report metadata: Lot, supplier, certificate of analysis snapshot, storage log, deviations, and raw data links.

FAQs (NLP‑Friendly, Answer‑First)

1) What is Vesugen (KED)?
Vesugen is a synthetic tripeptide (Lys–Glu–Asp) studied as a vascular and neuroprotective bioregulator that appears to modulate gene expression via DNA/histone interactions. Preclinical reports include normalization of endothelin‑1, restoration of connexins, and SIRT1 increases in endothelium, and dendritic support in neuronal models. (Khavinson)

2) How does KED influence gene expression?
KED influences gene expression through short‑peptide interactions with DNA and histones, a mechanism shown across ultrashort peptides, with KED specifically noted for potential histone/nucleosome binding and promoter docking (e.g., MKI67). This epigenetic route aligns with observed changes in endothelial and neuronal markers. (MDPI)

3) What outcomes are reported for vascular research?
Reported vascular outcomes include EDN1 normalization, connexin restoration, and increased SIRT1, consistent with improved endothelial communication and anti‑senescence signals in preclinical models of atherosclerosis/restenosis. These data are promising but require independent replication. (PubMed)

4) What outcomes are reported for brain/neuroplasticity research?
KED preserved dendritic spines and enhanced dendritic arborization in 5xFAD mice and neuronal cultures; gene markers for neurogenesis (e.g., NES, GAP43) and cell cycle (p16/p21) were modulated. Induced neurons from older donors showed improved dendritic metrics with KED exposure. (MDPI)

5) Is there clinical evidence for KED?
Human evidence is limited. A small Russian study recommended Pinealon and Vesugen as geroprotectors in geriatric practice, and a separate report described cognitive/functional improvements with combined use under specific conditions, but robust randomized trials are lacking and no mainstream regulatory approvals exist. (PubMed)

6) How should KED be stored and handled in the lab?
Store lyophilized peptide desiccated and cold (≤ −20 °C) and keep solutions cold and short‑lived per your SOP; avoid repeated freeze–thaw. Use BWFI (0.9% benzyl alcohol) for multi‑withdrawal research vials when appropriate. Validate stability with your own data. (PMC)

Evidence Highlights (Information Gain)

To help researchers map KED’s literature to outcomes of interest, below is a concise mechanism‑to‑marker mapping drawn from peer‑reviewed papers:

  • Vascular Homeostasis → EDN1, connexins (Cx37/Cx40/Cx43), SIRT1 shifts in endothelial models; potential benefit in atherosclerosis/restenosis contexts. Implication: microvascular tone/communication support. (PubMed)
  • Cell Proliferation → MKI67 promoter docking and Ki‑67 changes in endothelial/aging models. Implication: controlled proliferation under aging stressors. (PubMed)
  • Neuroplasticity → Dendritic spine preservation, dendritic arborization increases; regulation of NES, GAP43, p16/p21, and AD‑linked genes; likely histone interaction. Implication: structural substrates for plasticity. (MDPI)
  • Genome Engagement → DNA binding sequence GCCG listed for KED; short peptides can destabilize/reshape DNA locally and bind histone tails. Implication: sequence‑selective transcription cues. (Khavinson)

Stability/Handling Rationale: Pharmaceutical literature shows lyophilization + low temperature and, where applicable, lyoprotectants support peptide integrity; solutions are less stable and require stringent time/temperature control and aliquoting. Implication: plan your KED workflows to minimize hydrolysis/oxidation and aggregation. (PMC)

Next Steps

If you’re exploring vascular signaling, endothelial senescence, or dendritic morphology in aging/AD models, KED offers a compact, mechanistically rich probe to test epigenetic control → phenotype hypotheses alongside appropriate controls.

Bottom line: Vesugen (KED) is a small, epigenetically active research peptide with vascular and neuronal readouts worth testing in well‑controlled models—human claims remain preliminary and require rigorous trials. (PubMed)