Molecular Properties
| Parameter | Value |
|---|---|
| Chemical Name | Cortagen / AED Tripeptide |
| Amino Acid Sequence | Ala-Glu-Asp (AED) |
| Molecular Formula | C₁₂H₁₉N₃O₈ |
| Molecular Weight | 333.30 g/mol |
| CAS Number | Not assigned (research peptide bioregulator) |
| Sequence Length | 3 amino acids (tripeptide) |
| Bioregulator Class | Cerebral cortex peptide bioregulator; cognitive research compound |
Physical Properties
| Property | Specification |
|---|---|
| Appearance | White to off-white lyophilized powder |
| Solubility | Freely soluble in water, PBS, or saline at ≥5 mg/mL |
| pH (1% solution) | 4.0 - 6.0 (acidic due to Glu/Asp residues) |
| Hygroscopicity | Low; standard desiccated storage sufficient |
| Solution Stability | Stable at 4°C for 14-21 days; highly stable short peptide |
Analytical Specifications
| Test | Specification |
|---|---|
| HPLC Purity | ≥98.0% |
| Mass Spectrometry | Confirmed [M+H]⁺ = 333.30 ± 0.3 Da (or corresponding target sequence mass) |
| Peptide Content | ≥95% (by amino acid analysis) |
| Endotoxin Level | <1.0 EU/mg |
| Acetate Content | ≤5% |
| TFA Content | ≤0.1% |
| Water Content | ≤5% (Karl Fischer) |
Storage Parameters
| Condition | Specification |
|---|---|
| Lyophilized Storage | -20°C, desiccated (room temperature short-term acceptable) |
| Lyophilized Shelf Life | 36 months when stored properly at -20°C |
| Reconstituted Storage | 2-8°C for up to 21 days; -20°C for up to 6 months |
| Analytical Stock Preparation | Dissolve in sterile water or neutral buffer (PBS, pH 7.4) with gentle vortexing for 15-30 seconds |
| Freeze-Thaw Cycles | Tolerates 5+ cycles; short peptide backbone is highly stable |
| Light Sensitivity | Minimal; standard laboratory storage acceptable |
In Vitro & Preclinical Model Concentrations
| Experimental Model | Published Concentration / Regimen | Exposure Schedule | Administration Context |
|---|---|---|---|
| In Vitro Cortical Neuron Culture | 1-100 μM | Daily media change or continuous exposure | Culture media |
| Small Animal Models (Rodent) | 0.1-1 mg/kg | Daily for 10-20 days | SC, IP, intranasal in rodent studies |
| Rodent Learning & Memory Assays | 0.25-1 mg/kg | Daily for 14-30 days | SC or intranasal in rodent models |
| Preclinical Neuroplasticity Models | 0.5-2 mg/kg | 10-day experimental cycles | SC or IP in rodent models |
Note: Concentrations and animal regimens summarized above are extracted from published in vitro and rodent studies for laboratory reference only. Cortagen is intended strictly for laboratory research.
Key Research Studies
| Year | Study Focus | Key Findings |
|---|---|---|
| 2003 | Isolation and initial characterization | Cortagen isolated from brain cortex extracts; demonstrated neuroprotective activity in vitro at 10-100 μM; reduced neuronal apoptosis by 35-50% in oxidative stress models |
| 2010 | Cognitive function and memory in aged rodents | Cortagen administration (0.5 mg/kg daily for 20 days) improved learning and memory performance in aged rodents; Morris water maze latency reduced by 30%; novel object recognition increased by 40% |
| 2015 | Gene expression profiling in cortical tissue | Microarray analysis revealed cortagen modulated 73 cortex-specific genes; upregulated synaptic genes (PSD-95, synaptophysin, synapsin-1), neurotrophic factors (BDNF, NT-3), and antioxidant enzymes |
| 2019 | Neuroplasticity and synaptic density | Treatment with cortagen (0.5 mg/kg for 15 days) increased dendritic arborization by 25% in rodent hippocampus and prefrontal cortex; enhanced spine density and synaptic protein expression; improved electrophysiological markers of LTP |
Mechanism of Action
| Biological Pathway | Description |
|---|---|
| Cortex-Specific Bioregulation | Short peptide derived from cerebral cortex tissue; exhibits preferential effects on cortical neurons; proposed chromatin interaction and epigenetic modulation |
| Gene Expression Modulation | Influences expression of cognition-related genes; upregulates synaptic plasticity proteins (Arc, Homer1, PSD-95); enhances neurotrophic factor production (BDNF, NGF) |
| Synaptic Enhancement | Increases synaptic protein synthesis; promotes dendritic spine formation and stabilization; enhances glutamatergic transmission and NMDA receptor function in preclinical models |
| Neuroprotection | Reduces oxidative stress and inflammation; upregulates antioxidant defense systems; protects against excitotoxicity and age-related neuronal damage in vitro and in rodent models |
| Duration of Effect | Cumulative effects observed over 10-20 days in rodent studies; molecular and structural changes persist 2-4 weeks post-treatment |
Quality Control Parameters
| Test Method | Acceptance Criteria |
|---|---|
| Appearance (visual) | White to off-white powder; fine uniform texture |
| Reconstitution Test | Complete dissolution within 30 seconds; clear colorless solution |
| RP-HPLC (purity) | Main peak ≥98.0%; no single impurity >0.5% |
| ESI-MS (identity) | [M+H]⁺ = 333.30 ± 0.3 Da confirmed |
| Amino Acid Sequence | Confirmed sequence by MS/MS fragmentation |
Bioregulator Comparison: Brain-Targeted Peptides
| Bioregulator | Sequence | Target Region | Primary Research Focus |
|---|---|---|---|
| Cortagen | Ala-Glu-Asp (AED) | Cerebral cortex | Cognitive function, learning, memory |
| Pinealon | Glu-Asp-Arg (EDR) | General brain/CNS | Neuroprotection, oxidative stress |
| Cerebrolysin components | Various peptides (<10 kDa) | Whole brain | Neurotrophic effects, stroke recovery models |
Structure-Activity Considerations
| Position | Amino Acid | Structural Role |
|---|---|---|
| 1 | Alanine (Ala) | Small hydrophobic residue; N-terminal; membrane permeability |
| 2 | Glutamic acid (Glu) | Acidic residue; central position; conformational flexibility |
| 3 | Aspartic acid (Asp) | Acidic residue; C-terminal; potential for electrostatic interactions |
| Net Charge | Negative at physiological pH (2 acidic residues, neutral N-terminus) | |
Experimental Application Guidelines
| Model System | Optimal Concentration / Dose | Duration |
|---|---|---|
| Primary Cortical Neurons | 10-50 μM | 24-72 hours |
| Neuroblastoma/Glioma Lines | 1-100 μM | 24-96 hours |
| Learning/Memory Tasks (rodent) | 0.25-0.5 mg/kg | 14-30 days before testing |
| Age-Related Cognitive Decline (rodent) | 0.5-1 mg/kg | 10-20 day cycles, repeated |
| Stroke/Injury Models (rodent) | 0.5-2 mg/kg | Initiated post-injury, 7-14 days |
Reported Biological Effects
| Effect Category | Observed Changes | Effective Concentration Range |
|---|---|---|
| Cognitive Performance (Rodent) | Improved spatial learning, working memory, attention; reduced cognitive decline in aged animal models | 0.25-1 mg/kg (in vivo) |
| Synaptic Markers | Increased PSD-95, synaptophysin, synapsin-1 expression; enhanced spine density | 10-50 μM (in vitro); 0.5 mg/kg (in vivo) |
| Neurotrophic Factors | Upregulated BDNF, NGF, NT-3 levels; enhanced TrkB signaling | 10-100 μM (in vitro); 0.5-1 mg/kg (in vivo) |
| Oxidative Stress | Reduced ROS, lipid peroxidation; increased SOD, catalase, GSH-Px activity | 10-50 μM (in vitro); 0.5-2 mg/kg (in vivo) |
Regulatory & Compounding Status
Cortagen is an unapproved investigational research peptide studied primarily in Russian and Eastern European bioregulator research programs. It is not approved by the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA) for human or veterinary therapeutic or diagnostic use, and does not appear on FDA’s 503A or 503B bulk drug substances eligible lists. This monograph is intended strictly for laboratory research and educational reference.
External References
- Khavinson VKh, et al. Short peptides regulate gene expression. Bull Exp Biol Med. 2011;151(3):288-92. https://link.springer.com/article/10.1007/s10517-011-1316-z
- Khavinson VKh, et al. Peptides and ageing. Neuro Endocrinol Lett. 2003;24(3-4):144-6. https://pubmed.ncbi.nlm.nih.gov/14523353/
- National Center for Biotechnology Information. Bioactive Peptides in Brain Function and Disease. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485952/