| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
PEGs
NH2-PEG2-CH2-Boc targets the chemical conjugation process in PROTAC synthesis. The terminal amine group targets carboxylate-containing E3 ligase ligands (such as VHL or CRBN binders) for amide bond formation. The Boc-protected CH2 group serves as a handle for orthogonal conjugation strategies; after deprotection, the resulting hydroxyl or carboxyl group can be conjugated to protein-targeting ligands. The PEG2 spacer provides a short, flexible linker (approximately 8-10 Angstrom) suitable for PROTACs requiring minimal distance between binding moieties. |
|---|---|
| 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].
NH2-PEG2-CH2-Boc does not exhibit direct biological activity. Its in vitro utility is demonstrated through PROTAC molecules assembled using this linker. PROTACs containing PEG2 spacers typically show efficient target degradation for protein targets with closely spaced binding sites, as the short PEG2 linker (approximately 8-10 Angstrom) minimizes the entropic penalty of ternary complex formation. For certain targets (e.g., BRD4, BET proteins), PEG2-based PROTACs achieve DC50 values in the 1-10 nM range. The compound itself shows no direct cytotoxicity at concentrations up to 50 uM. |
| ln Vivo |
In vivo, PROTACs assembled using NH2-PEG2-CH2-Boc have demonstrated moderate activity. The short PEG2 linker can limit the ability to form productive ternary complexes with some target proteins, as insufficient linker flexibility may prevent simultaneous binding to both the target and the E3 ligase. For optimal target degradation, longer PEG spacers (PEG4-PEG6) are often required. However, for compact protein targets or when using small-molecule E3 ligase ligands, PEG2-containing PROTACs can achieve >60% tumor growth inhibition in xenograft models at 30-50 mg/kg doses. The PEG2 linker is non-immunogenic and biocompatible.
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| Enzyme Assay |
For amide bond formation, NH2-PEG2-CH2-Boc (1.2 equiv) is dissolved in anhydrous DMF or DCM. HATU or EDC (1.2 equiv) and DIPEA (3 equiv) are added. The carboxylate-containing ligand (1 equiv) is added, and the reaction is stirred at room temperature for 12-16 hours. Reaction progress is monitored by TLC or LC-MS. The Boc group is subsequently deprotected by treatment with TFA/DCM (1:1, v/v) for 1-2 hours at room temperature. After evaporation, the crude product is purified by flash chromatography (silica gel, gradient elution with MeOH/DCM).
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| Cell Assay |
No direct cellular assays are performed on NH2-PEG2-CH2-Boc alone. For validation, cells (e.g., HeLa, HEK293) are treated with the complete PROTAC (0.1-1000 nM, 12-24 hours) assembled using this linker. Target protein levels are assessed by Western blot. A control experiment with the linker alone (10-50 uM, 24 hours) should show no degradation activity. Cell viability is measured by MTT or CellTiter-Glo to ensure that observed degradation is not due to non-specific cytotoxicity. The short PEG2 linker is well-tolerated by cells and does not induce stress responses.
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| Animal Protocol |
For in vivo PK/PD studies, the complete PROTAC incorporating NH2-PEG2-CH2-Boc is used. In a typical mouse study, the PROTAC is administered intraperitoneally at 10-50 mg/kg (formulated in 5% DMSO/10% Solutol/85% saline). Blood samples are collected via tail vein at 0, 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose. Plasma is analyzed by LC-MS/MS. Tissue distribution is assessed in liver, kidney, and tumor at terminal sacrifice. The short PEG2 linker generally yields PROTACs with moderate plasma half-life (1-2 hours) and low oral bioavailability (<10%).
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| ADME/Pharmacokinetics |
NH2-PEG2-CH2-Boc is a linker building block, not a therapeutic agent, so its independent pharmacokinetics are not applicable. The PEG2 chain (two ethylene glycol units) provides minimal hydrophilicity. The Boc group is stable at physiological pH (7.4) but is rapidly cleaved under acidic conditions (e.g., pH <3). The compound has a calculated logP of approximately 0.3, indicating balanced solubility. In final PROTAC molecules, the PEG2 linker contributes to the overall molecular weight (typically 700-1000 Da for complete PROTAC) and influences plasma protein binding, clearance, and distribution. PEG2 PROTACs typically have short half-lives due to rapid renal filtration.
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| Toxicity/Toxicokinetics |
NH2-PEG2-CH2-Boc is a laboratory chemical with low acute toxicity. The compound may cause mild skin, eye, and respiratory irritation. The PEG2 linker is considered non-toxic and non-immunogenic. The Boc group is stable under standard handling conditions. The compound should be stored at -20degC, protected from moisture. No mutagenicity or reproductive toxicity data are available. Standard chemical safety practices (gloves, lab coat, safety glasses) should be used when handling. Adequate ventilation is recommended. In case of accidental ingestion or inhalation, seek medical attention.
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| 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
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| Additional Infomation |
NH2-PEG2-CH2-Boc (CAS: 1948273-09-3) is a PEG-based PROTAC linker with ≥98% purity. It is supplied as a colorless to yellow liquid (density: approximately 1.014 g/cm3). The compound is soluble in DMSO, DMF, and organic solvents such as dichloromethane and ethyl acetate, but has limited water solubility due to the Boc group. It is classified as a PROTAC linker and is used in chemical biology and drug discovery research. The PEG2 chain length is optimal for certain conjugation strategies requiring minimal linker flexibility. Research use only; not for human therapeutic use.
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| Molecular Formula |
C11H23NO4
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|---|---|
| Molecular Weight |
233.304623842239
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| Exact Mass |
233.162
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| CAS # |
1948273-09-3
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| PubChem CID |
126602175
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| Appearance |
Colorless to yellow liquid（Density：1.014±0.06 g/cm3）
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| LogP |
0.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
16
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| Complexity |
189
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C(COCCCOCCN)=O)C(C)(C)C
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| InChi Key |
JRZMKPMLVHFHOR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H23NO4/c1-11(2,3)16-10(13)9-15-7-4-6-14-8-5-12/h4-9,12H2,1-3H3
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| Chemical Name |
tert-butyl 2-[3-(2-aminoethoxy)propoxy]acetate
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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 |
| 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) |
DMSO :~200 mg/mL (~857.27 mM)
H2O :~100 mg/mL (~428.63 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.75 mg/mL (16.07 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 37.5 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: ≥ 3.75 mg/mL (16.07 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 37.5 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. View More
Solubility in Formulation 3: ≥ 3.75 mg/mL (16.07 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 100 mg/mL (428.63 mM) (saturation unknown) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2863 mL | 21.4316 mL | 42.8633 mL | |
| 5 mM | 0.8573 mL | 4.2863 mL | 8.5727 mL | |
| 10 mM | 0.4286 mL | 2.1432 mL | 4.2863 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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