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| 5mg |
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| 10mg |
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| Targets |
Transdermal Peptide Disulfide TFA specifically binds to the Na+/K+-ATPase beta-subunit (ATP1B1), and it mainly interacts with the C-terminus of ATP1B1 [27L21-L23]. This binding targets the sodium-potassium pump, which is crucial for maintaining the ionic gradient across cell membranes. By interacting with this protein, the peptide disrupts the tight junctions and structural integrity of the epidermal layer, creating paracellular pathways that allow macromolecules to pass through the skin. This mechanism enhances the transdermal delivery of a wide range of macromolecules, such as proteins and siRNAs, that are otherwise poorly absorbed through the skin.
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| ln Vitro |
Cells will upregulate the amount of ATP1B1 to preserve function and structure in the presence of Transdermal Peptide Disulfide due to the particular binding of Transdermal Peptide Disulfide to ATP1B1; thus, the expression of ATP1B1 increases. But with time, some Transdermal Peptide Disulfide molecules would enter cells through endocytosis; as a result, ATP1B1 expression would decline. The way Transdermal Peptide Disulfide and ATP1B1 interact modifies not only the expression of ATP1B1, but also where it is located and ultimately the epidermal layer's structure. Inhibitors or competitors may lessen this interaction, which would decrease the amount of macromolecular medications that are delivered via the skin[1].
In vitro studies demonstrate the peptide's unique ability to reversibly enhance skin permeability. When applied to human skin cells in culture, Transdermal Peptide Disulfide binds to its target, ATP1B1. As a result, cells initially upregulate ATP1B1 levels to maintain function, but over time, the peptide is internalized by endocytosis, leading to a subsequent decrease in ATP1B1 expression. This interaction also changes the localization of ATP1B1 and alters the structure of the epidermal layer, which can be measured by changes in transepithelial electrical resistance (TEER) across a cell monolayer. This disruption is directly responsible for the enhanced delivery of macromolecular drugs, and this effect can be specifically blocked by peptide inhibitors or competitors [27L26-L36]. |
| ln Vivo |
In vivo activity of the peptide has been demonstrated in animal models, primarily focusing on its ability to enhance the absorption of co-administered drugs. In mouse or rat models, applying a formulation containing Transdermal Peptide Disulfide along with a model macromolecule (e.g., insulin, human growth hormone) to the skin results in significantly higher systemic levels of the macromolecule in the bloodstream compared to application without the peptide. The peptide facilitates the paracellular transport of these otherwise non-permeable molecules across the stratum corneum, the skin's main barrier layer, allowing them to reach systemic circulation and exert their therapeutic effects.
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| Enzyme Assay |
The interaction of the peptide with its ATP1B1 target is typically studied using surface plasmon resonance (SPR) or enzyme-linked immunosorbent assay (ELISA). A typical binding assay involves immobilizing the recombinant ATP1B1 protein on a sensor chip or microplate well. The Transdermal Peptide Disulfide is then flowed over the immobilized protein at various concentrations. The binding affinity is measured by the association and dissociation rates, allowing for the calculation of a binding constant (KD). This can be further characterized using competition assays where unlabeled peptide is used to displace a labeled peptide in order to determine its specificity.
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| Cell Assay |
For in vitro cell-based assays, keratinocytes (the primary cell type in the epidermis) are cultured on permeable Transwell inserts to form a tight barrier that mimics human skin. Once the monolayer is established, the cells are treated with the peptide (e.g., 10-100 microM) in the apical compartment. The integrity of the cell monolayer is monitored over time by measuring the TEER using an epithelial volt-ohmmeter. A decrease in TEER indicates the disruption of tight junctions, which correlates with increased paracellular permeability. The transport of fluorescently labeled macromolecules (e.g., FITC-dextran) from the apical to the basolateral compartment can be directly measured in the same system using a fluorescence plate reader.
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| Animal Protocol |
In vivo studies are typically performed using rodent models (mice or rats). A typical protocol involves shaving an area of skin on the animal's back. A solution containing the macromolecule of interest (e.g., insulin at 5 mg/kg) is mixed with the Transdermal Peptide Disulfide (e.g., at 0.5-2 mg/kg). This mixture is then applied topically to the shaved area. Blood samples are collected via the tail vein at predetermined time points (0, 30, 60, 120, and 240 minutes post-application). The concentration of the macromolecule in the serum is then measured by ELISA or LC-MS. An increase in the serum concentration of the macromolecule in the peptide-treated group compared to the control group demonstrates enhanced transdermal delivery.
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| ADME/Pharmacokinetics |
As a peptide, Transdermal Peptide Disulfide TFA is not intended for systemic delivery but rather as a local enhancer. Its pharmacokinetic properties are not typically characterized. When applied topically, the peptide resides primarily in the stratum corneum and epidermis. Some peptide molecules may be transported into cells by endocytosis, leading to its internalization and eventual degradation, which limits its duration of action [27L30-L31]. Its molecular weight is 1175.17 g/mol. The TFA salt form improves the peptide's solubility and stability during storage and handling, making it easier to formulate into a topical solution for research use [27L38].
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| Toxicity/Toxicokinetics |
Safety and toxicity studies of this transdermal peptide are limited to research settings. However, given its function, the safety profile is likely favorable, as the peptide's effect is localized and reversible. The effect of the peptide on skin barrier integrity can be attenuated by the removal of the peptide, leading to restoration of the skin barrier. Acute toxicity is considered low, as the primary mode of action is a physical disruption of the stratum corneum. As with all research chemicals, standard safety precautions should be followed. It is not for human or clinical use and is strictly a laboratory research tool.
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| References | |
| Additional Infomation |
Transdermal Peptide Disulfide TFA (TD 1 Disulfide) is a chemical tool for research into non-invasive drug delivery systems. It is a cell-penetrating peptide that is very effective at enhancing transdermal delivery of macromolecules through skin. This peptide is supplied as a TFA salt, which enhances its solubility and stability. The compound has a molecular weight of 1175.17, a purity of typically ≥98%, and is stored as a solid at -20degC, protected from light. This compound is strictly for research applications, not for human or clinical use. Its utility has been demonstrated by its ability to significantly enhance the transdermal delivery of a variety of macromolecules, including proteins and other large molecules.
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| Molecular Formula |
C42H65F3N14O18S2
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| Molecular Weight |
1175.17
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| Related CAS # |
Transdermal Peptide Disulfide;888486-23-5
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
H2O :~100 mg/mL (~85.09 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (85.09 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8509 mL | 4.2547 mL | 8.5094 mL | |
| 5 mM | 0.1702 mL | 0.8509 mL | 1.7019 mL | |
| 10 mM | 0.0851 mL | 0.4255 mL | 0.8509 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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