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Gamma-glutamylcysteine (TFA) is an intermediate for synthesis of glutathione (GSH). It is a dipeptide acting as an essential cofactor for the antioxidant enzyme glutathione peroxidase (GPx). It can also increase anti-inflammatory cytokines such as IL-10 and reduce pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β).
Physicochemical Properties
| Molecular Formula | C10H15F3N2O7S |
| Molecular Weight | 364.29551243782 |
| Exact Mass | 364.055 |
| CAS # | 283159-88-6 |
| Related CAS # | Gamma-glutamylcysteine;636-58-8 |
| PubChem CID | 139035037 |
| Appearance | White to off-white solid powder |
| Hydrogen Bond Donor Count | 6 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 23 |
| Complexity | 367 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | SCC(C(=O)O)NC(CCC(C(=O)O)N)=O.FC(C(=O)O)(F)F |
| InChi Key | WBAPFIMTGPKLNF-FHAQVOQBSA-N |
| InChi Code | InChI=1S/C8H14N2O5S.C2HF3O2/c9-4(7(12)13)1-2-6(11)10-5(3-16)8(14)15;3-2(4,5)1(6)7/h4-5,16H,1-3,9H2,(H,10,11)(H,12,13)(H,14,15);(H,6,7)/t4-,5-;/m0./s1 |
| Chemical Name | (2S)-2-amino-5-[[(1R)-1-carboxy-2-sulfanylethyl]amino]-5-oxopentanoic acid;2,2,2-trifluoroacetic acid |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets |
- Glutathione (GSH) biosynthesis pathway (serves as GSH precursor) [1] - Reactive oxygen species (ROS) generation [1] - Nuclear factor-κB (NF-κB) signaling pathway [1] - Pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) [1] |
| ln Vitro |
- Gamma-glutamylcysteine (TFA) (GGC) ameliorated Aβ40 oligomer-induced oxidative damage in human astrocytes. At concentrations of 100, 200, 400 μM, it increased intracellular GSH levels by 35±3%, 62±4%, and 88±5%, respectively, compared to Aβ40-treated group [1] - It reduced Aβ40-induced ROS production: 400 μM GGC decreased ROS levels by 72±6% [1] - The compound inhibited neuroinflammation: 400 μM reduced TNF-α, IL-6, and IL-1β mRNA levels by 65±5%, 68±4%, and 61±5%, and protein levels by 59±4%, 63±4%, and 57±3%, respectively [1] - It suppressed Aβ40-induced NF-κB activation: 400 μM decreased IκBα phosphorylation by 58±4% and NF-κB p65 nuclear translocation by 55±3% [1] - It protected human astrocyte viability: 400 μM improved cell viability from 62±3% (Aβ40 group) to 89±4% [1] - No significant cytotoxicity was observed in human astrocytes at concentrations up to 800 μM [1] |
| Enzyme Assay |
- ROS detection assay: Human astrocytes were pretreated with Gamma-glutamylcysteine (TFA) (100, 200, 400 μM) for 24 hours, then exposed to Aβ40 oligomers for 24 hours. Cells were loaded with a ROS-specific fluorescent probe, incubated for 30 minutes, and fluorescence intensity was measured at 488/525 nm to quantify ROS levels [1] - GSH quantification assay: Treated astrocytes were lysed, and the lysate was mixed with GSH detection reagent. After incubation at 37°C for 15 minutes, absorbance was measured at 412 nm to determine GSH concentration [1] - NF-κB activity assay: Nuclear extracts from treated cells were prepared, and NF-κB DNA-binding activity was measured using an electrophoretic mobility shift assay (EMSA) [1] |
| Cell Assay |
- Human astrocyte protection assay: Cells were seeded in 96-well plates (5×10³ cells/well) and 6-well plates (2×10⁵ cells/well). After overnight incubation, cells were pretreated with Gamma-glutamylcysteine (TFA) (100, 200, 400 μM) for 24 hours, then stimulated with Aβ40 oligomers for 24 hours. Cell viability was measured by MTT assay; cytokine mRNA levels by RT-PCR; cytokine proteins and NF-κB pathway proteins by Western blot [1] - Cytotoxicity assay: Human astrocytes were treated with Gamma-glutamylcysteine (TFA) (200, 400, 600, 800 μM) for 48 hours, and cell viability was measured by MTT assay [1] |
| Toxicity/Toxicokinetics |
- Gamma-glutamylcysteine (TFA) showed no significant cytotoxicity to human astrocytes at concentrations up to 800 μM, with cell viability maintained above 90% [1] |
| References |
[1]. The Precursor to Glutathione (GSH), γ-Glutamylcysteine (GGC), Can Ameliorate Oxidative Damage and Neuroinflammation Induced by Aβ40 Oligomers in Human Astrocytes. Front Aging Neurosci. 2019 Aug 8;11:177. |
| Additional Infomation |
- Gamma-glutamylcysteine (TFA) is the rate-limiting precursor of glutathione (GSH), a key intracellular antioxidant [1] - Its neuroprotective mechanism involves replenishing GSH to scavenge excess ROS, and inhibiting the NF-κB signaling pathway to reduce neuroinflammation induced by Aβ40 oligomers [1] - It targets human astrocytes, which play a critical role in maintaining brain redox homeostasis and modulating neuroinflammation, suggesting potential therapeutic value for Alzheimer's disease and other neurodegenerative disorders [1] - The TFA (trifluoroacetate) moiety is a counterion for the GGC molecule, facilitating its solubility and stability in experimental applications [1] |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~274.50 mM) H2O : ~100 mg/mL (~274.50 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.86 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.86 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7450 mL | 13.7250 mL | 27.4499 mL | |
| 5 mM | 0.5490 mL | 2.7450 mL | 5.4900 mL | |
| 10 mM | 0.2745 mL | 1.3725 mL | 2.7450 mL |