m-PEG2-4-nitrophenyl carbonate is a PEG-based activated carbonate linker designed for stepwise PROTAC assembly via nucleophilic substitution. Structurally, it comprises a short polyethylene glycol chain terminating in a carbonate that is pre-activated by a 4-nitrophenyl leaving group, enabling efficient transfer of the carbonate to amine or other nucleophilic handle-bearing partners under standard organic coupling conditions. The resulting linkage provides a stable, modular connection while retaining PEG’s beneficial effects on solubility and reduced nonspecific aggregation, which are commonly important for maintaining productive ternary complex formation in targeted protein degradation workflows. In PROTAC design, this linker functions as a “reactive handle” that allows researchers to conjugate a PEG spacer between a targeting ligand and an E3 ligase-binding module, thereby tuning spatial geometry and flexibility to improve degradation potency and selectivity. Its use supports reproducible synthesis of well-defined conjugates for structure–activity relationship studies and mechanistic evaluation of degradation pathways.
Structure of 105108-59-6
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This m-PEG2-4-nitrophenyl carbonate is a PEG-based PROTAC linker component designed to enable efficient conjugation between targeting ligands and reactive handles. Its carbonate functionality supports controlled linker installation, while the aryl leaving group facilitates nucleophilic substitution under PROTAC-relevant coupling workflows. The PEG spacer can improve solubility and tune the effective distance between binding elements, supporting robust targeted protein degradation strategies. The following sections describe the structure and practical reactivity considerations in detail below.
Structure: The linker contains a PEG ether segment connected through a carbonate linkage to a meta-substituted aromatic ring bearing a nitro group. It features an O-alkyl ether chain, a carbonate C–O framework, and an activated aryl leaving group. These elements collectively provide flexibility and favorable hydrophilicity for PROTAC assembly.
Reactivity: The carbonate can undergo nucleophilic acyl substitution, where nucleophiles such as amines or other suitable oxygen/nitrogen nucleophiles displace the nitrophenyl leaving group to form a new carbonate or related acylated linkage. Coupling is typically performed under anhydrous or low-water conditions using compatible bases to promote nucleophile generation, with polar aprotic solvents commonly employed to maintain solubility and reaction control. Reaction progress is monitored by standard analytical methods, and purification is used to remove unreacted linker and byproducts.
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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