| Size | Price | |
|---|---|---|
| 1g | ||
| Other Sizes |
| Targets |
PEGs
PROTAC Linkers. |
|---|---|
| ln Vitro |
One ligand is for an E3 ubiquitin ligase, and the other is for the target protein; these two ligands are joined by a linker to form PROTACs. The intracellular ubiquitin-proteasome system is utilized by PROTACs to specifically destroy target proteins[1].
As a linker molecule, Bis-PEG6-t-butyl ester itself has no intrinsic biological activity; it serves as a structural connector to join two ligands (e.g., two target protein ligands or two E3 ligase ligands) in the synthesis of PROTAC molecules or other bioconjugates. The t-butyl ester groups are acid-labile protecting groups that can be removed under acidic conditions (e.g., with TFA) to reveal carboxylic acids. These free carboxylic acids can then be activated with EDC and NHS to form amide bonds with primary amine-containing ligands. The PEG6 spacer provides flexibility and water solubility, which facilitates the formation of the ternary complex required for targeted protein degradation. |
| ln Vivo |
No specific in vivo activity has been reported for this linker alone; its activity is derived from the final PROTAC molecule after conjugation with appropriate ligands. The in vivo efficacy of a complete PROTAC is determined in animal models.
|
| Enzyme Assay |
N/A; this compound is not assessed in isolated enzyme/receptor binding assays. As a synthetic intermediate, its quality is typically confirmed by analytical methods such as HPLC and NMR, with a standard purity of ≥95%. The t-butyl ester protecting groups can be characterized by NMR spectroscopy (singlet around 1.4-1.5 ppm). The PEG6 spacer can be confirmed by mass spectrometry.
|
| Cell Assay |
N/A; this linker is not tested alone in cell-based assays. It is used as a building block for constructing PROTACs. In a typical two-step synthesis, the t-butyl ester groups are first removed using TFA to generate a di-carboxylic acid. The free carboxylic acids are then activated with EDC and NHS and reacted with primary amine-containing ligands (e.g., target protein ligands or E3 ligase ligands) to form amide bonds. The resulting conjugate is then tested in cells for its biological activity. For PROTAC applications, the conjugate would be tested for target degradation.
|
| Animal Protocol |
N/A; no animal studies are performed with the linker alone. For a complete PROTAC conjugate, in vivo studies are conducted following institutional guidelines. The compound is typically formulated using a vehicle containing DMSO, PEG300, Tween-80, and saline and administered via intraperitoneal (IP) or intravenous (IV) injection. The PEG6 spacer may improve the pharmacokinetic properties of the conjugate by enhancing water solubility and reducing aggregation.
|
| ADME/Pharmacokinetics |
This compound has a molecular weight of 450.57, a molecular formula of C22H42O9, and a standard purity of ≥95%. The IUPAC name is di-tert-butyl 3,3′-((oxybis(ethane-2,1-diyl))bis(oxy))dipropionate (PEG6). It appears as a solid at room temperature. For storage, it should be kept at -20degC for up to 3 years, sealed, away from moisture. It is soluble in DMSO and other organic solvents. The t-butyl ester groups are stable under neutral and basic conditions but are acid-labile, so exposure to strong acids should be avoided. CAS: 439114-12-2.
|
| Toxicity/Toxicokinetics |
This product is for research use only and is not for human or veterinary use. Standard chemical safety precautions should be observed during handling. For research and further manufacturing use only, not for direct human use. This compound is not an approved drug and has not been cleared for clinical use.
|
| References |
[1]. An S, et al. Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs. EBioMedicine. 2018 Oct;36:553-562
|
| Additional Infomation |
The homobifunctional nature of Bis-PEG6-t-butyl ester allows for the synthesis of symmetric PROTAC molecules (where both ends are conjugated to the same type of ligand, e.g., a homodimeric PROTAC) or the conjugation of two different ligands in a stepwise manner after sequential deprotection and activation. The PEG6 spacer provides a longer, more flexible hydrophilic linker compared to PEG3 or PEG4, which may be optimal for target-E3 ligase pairs requiring a greater distance between binding sites. This compound is a valuable building block for PROTAC development and bioconjugation chemistry.
|
| Molecular Formula |
C22H42O9
|
|---|---|
| Molecular Weight |
450.56
|
| Exact Mass |
450.283
|
| CAS # |
439114-12-2
|
| PubChem CID |
18374579
|
| Appearance |
Colorless to light yellow liquid（Density：1.046±0.06 g/cm3）
|
| LogP |
2.533
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
22
|
| Heavy Atom Count |
31
|
| Complexity |
425
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(C)(C)OC(=O)CCOCCOCCOCCOCCOCCC(=O)OC(C)(C)C
|
| InChi Key |
RYJCLSVRARTBFI-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H42O9/c1-21(2,3)30-19(23)7-9-25-11-13-27-15-17-29-18-16-28-14-12-26-10-8-20(24)31-22(4,5)6/h7-18H2,1-6H3
|
| Chemical Name |
tert-butyl 3-[2-[2-[2-[2-[3-[(2-methylpropan-2-yl)oxy]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoate
|
| 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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 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 | 2.2195 mL | 11.0973 mL | 22.1946 mL | |
| 5 mM | 0.4439 mL | 2.2195 mL | 4.4389 mL | |
| 10 mM | 0.2219 mL | 1.1097 mL | 2.2195 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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