| Targets |
Mal-PEG2-oxyamine TFA does not target a specific biological receptor but serves as a chemical crosslinker. In PROTAC design, the linker connects an E3 ubiquitin ligase ligand with a target protein ligand, enabling selective protein degradation via the ubiquitin-proteasome system. The maleimide group reacts with cysteine thiols, while the oxyamine group reacts with carbonyls (aldehydes/ketones) to form stable oxime bonds, providing orthogonal conjugation chemistry.
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| ln Vitro |
PROTACs contain two different ligands connected by a linker; one is a ligand for an E3 ubiquitin ligase and the other is for the target protein. PROTACs exploit the intracellular ubiquitin-proteasome system to selectively degrade target proteins[1].
In vitro, Mal-PEG2-oxyamine TFA is used as a modular linker in the assembly of PROTACs and ADCs. The discrete PEG2 spacer (~9-10 backbone atoms) provides optimal flexibility and solubility while maintaining a distinct constrained geometry compared to PEG3 or PEG4 variants. This precise spacer length can influence PROTAC ternary complex formation efficiency and bioconjugate performance. The TFA salt form ensures stable stock for multi-parallel synthesis applications. |
| ln Vivo |
In vivo applications of Mal-PEG2-oxyamine TFA are indirect, as the compound itself is not administered therapeutically. Rather, it is used to synthesize PROTACs or ADCs that are then evaluated in vivo for targeted protein degradation or anticancer efficacy. The linker's stability and orthogonal reactivity enable the construction of bioconjugates with defined pharmacokinetic and pharmacodynamic profiles suitable for in vivo studies.
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| Enzyme Assay |
Non-cellular assays for Mal-PEG2-oxyamine TFA involve characterizing its conjugation efficiency and stability. The maleimide-thiol conjugation can be monitored by HPLC or mass spectrometry to confirm successful coupling. The oxyamine-carbonyl oxime formation can be assessed under various pH conditions. Stability studies comparing the TFA salt versus free base forms demonstrate that the salt form prevents degradation during storage. Binding interactions are not applicable as this is a chemical linker.
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| Cell Assay |
In vitro cellular experiments using Mal-PEG2-oxyamine TFA typically involve treating cells with PROTACs or ADCs synthesized using this linker. Cellular assays assess target protein degradation (by Western blotting), cell viability (by MTT or CellTiter-Glo), and apoptosis induction. The linker's role is to enable the formation of functional bioconjugates; its own cellular effects are minimal. The orthogonal conjugation chemistry allows for site-specific labeling of antibodies or proteins.
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| Animal Protocol |
In vivo animal experiments are performed with PROTACs or ADCs synthesized using Mal-PEG2-oxyamine TFA, not with the linker itself. These studies are conducted in murine xenograft models to evaluate antitumor efficacy, pharmacokinetics, and safety of the final bioconjugates. The linker's contribution to the overall stability and performance of the conjugate is assessed through these studies.
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| ADME/Pharmacokinetics |
As a chemical linker, Mal-PEG2-oxyamine TFA has a molecular formula of C12H17F3N2O7 and a molecular weight of 358.27 g/mol. Purity is typically ≥95%. The compound is stored as a powder at -20°C under inert atmosphere to maintain stability. The TFA salt form is stable and prevents degradation of the oxyamine moiety. It is soluble in DMSO and other organic solvents suitable for bioconjugation reactions.
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| Toxicity/Toxicokinetics |
Toxicity data for Mal-PEG2-oxyamine TFA are limited as it is a research reagent used in bioconjugation, not a therapeutic agent. Standard laboratory safety precautions should be followed when handling this compound. The maleimide group is reactive and may cause skin sensitization. The compound is for research use only and not for human therapeutic applications. Researchers should consult the safety data sheet for specific handling and disposal guidelines.
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| Additional Infomation |
Mal-PEG2-oxyamine TFA is identified by the synonym 1-[2-[2-(2-aminooxyethoxy)ethoxy]ethyl]pyrrole-2,5-dione;2,2,2-trifluoroacetic acid. The CAS number is not specified in the available documentation. The discrete PEG2 spacer provides distinct advantages over longer PEG linkers for certain PROTAC applications. The TFA salt formulation is explicitly recommended over the free base form due to stability concerns. All products are for research use only.
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| Molecular Formula |
C12H17F3N2O7
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|---|---|
| Molecular Weight |
358.27
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| Appearance |
Colorless to light yellow liquid
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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) |
Typically soluble in DMSO (e.g. 10 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7912 mL | 13.9560 mL | 27.9119 mL | |
| 5 mM | 0.5582 mL | 2.7912 mL | 5.5824 mL | |
| 10 mM | 0.2791 mL | 1.3956 mL | 2.7912 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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