Hydroxy-PEG3-t-butyl ester

 CAS No.: 186020-66-6  Cat No.: BP-500049  Purity: ≥95% 4.5  

Hydroxy-PEG3-t-butyl ester is a polyethylene glycol–based linker bearing a terminal hydroxyl group and a protected carboxylate as a tert-butyl ester. Structurally, it provides a short, flexible PEG chain that can be used to introduce hydrophilicity and spatial separation between a target-binding ligand and an E3-recruiting moiety, while the ester protection enables controlled downstream functionalization. In PROTAC architectures, such linkers are employed to tune the effective distance and relative orientation of the interacting components, thereby improving the probability of productive ternary complex formation and stabilizing the conjugate in biological media. The terminal hydroxyl functionality allows convenient conjugation strategies (e.g., derivatization to reactive handles for coupling), and the tert-butyl ester can serve as a masked carboxyl group for later deprotection and attachment to other fragments. This makes Hydroxy-PEG3-t-butyl ester a practical building block for systematic linker optimization in targeted protein degradation research.

Hydroxy-PEG3-t-butyl ester

Structure of 186020-66-6

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Category
PROTAC Linker
Molecular Formula
C13H26O6
Molecular Weight
278.34
Related CAS
1186025-29-5 (polymer) 892154-71-1 (polymer)
Appearance
Colorless to light yellow to light orange clear liquid

* For research and manufacturing use only. Not for human or clinical use.

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Purity
≥95%
Solubility
Soluble in DMSO (10 mm)
Appearance
Colorless to light yellow to light orange clear liquid
Storage
Store at 2-8°C
Shipping
Room temperature, or blue ice upon request.
IUPACName
tert-butyl 3-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]propanoate
Synonyms
HO-PEG3-CH2CH2COOtBu; Hydroxy-PEG3-(CH2)2-Boc; OH-PEG3-TBA; OH-PEG3-CH2CH2COOtBu; HO-PEG3-t-butyl ester; tert-Butyl 12-hydroxy-4,7,10-trioxadodecanoate; 3-[2-[2-(2-Hydroxyethoxy)ethoxy]ethoxy]propionic acid tert-butyl ester; 12-Hydroxy-4,7,10-trioxadodecanoic Acid tert-Butyl Ester; 2-Methyl-2-propanyl 3-{2-[2-(2-hydroxyethoxy)ethoxy]ethoxy}propanoate; Propanoic acid, 3-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]-, 1,1-dimethylethyl ester; tert-Butyl triethylene glycol-O-propionate
Boiling Point
365.8±27.0°C (Predicted)
Density
1.052 g/mL at 20°C
InChI Key
KSXVEOLRERRELV-UHFFFAOYSA-N
InChI
InChI=1S/C13H26O6/c1-13(2,3)19-12(15)4-6-16-8-10-18-11-9-17-7-5-14/h14H,4-11H2,1-3H3
SMILES
CC(C)(C)OC(=O)CCOCCOCCOCCO
Biological Activity
Hydroxy-PEG2-(CH2)2-Boc is a uncleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Hydroxy-PEG2- (CH2)2-Boc is extracted from patent WO2004008101A2 (compound 196)[1] . In Vitro: ADCs are comprised of an antibody to which is attached an ADC cytotoxin through an ADC linker.

Hydroxy-PEG3-t-butyl ester is a polyethylene glycol (PEG)-based PROTAC linker building block designed to provide aqueous compatibility, conformational flexibility, and tunable spacing between ligands. Its PEG segment supports favorable solubility and reduced nonspecific interactions, while the protected carboxylate functionality enables controlled downstream conjugation to assemble targeted protein degraders. The structure and reactivity considerations for constructing PROTACs are described in detail below.

Structure: The linker contains an ether-rich PEG chain featuring a terminal hydroxyl group and a tert-butyl ester-protected carboxylate. It includes polar ether linkages, an ester carbonyl, and a tert-butyl group that masks the acidic functionality. Overall, it exhibits high hydrophilicity and flexible conformational behavior.

Reactivity: The tert-butyl ester is suitable for acid-mediated deprotection to reveal a reactive carboxylic acid for amide or ester coupling to PROTAC ligands. Typical construction strategies involve activating the liberated acid using standard coupling chemistries and forming stable linkages under mild, anhydrous conditions. Deprotection commonly uses dilute acid in organic or mixed solvents, followed by base-neutralization and purification prior to conjugation.

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It is commonly abbreviated as: C1V1 = C2V2

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Tip: Chemical formula is case sensitive. C22H30N4O c22h30n40
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