N-(Azido-PEG4)-N-bis(PEG4-acid)
CAS No.: 2093152-80-6
Cat No.: BP-501416
Purity: 98%
4.5 
N-(Azido-PEG4)-N-bis(PEG4-acid) is a heterobifunctional, PEG-based PROTAC linker containing an azide handle and two terminal carboxylic acid–terminated PEG4 arms. Structurally, it provides a flexible hydrophilic spacer network that can reduce steric constraints between a ligand and an E3-recruiting moiety while maintaining solubility in aqueous buffers. The azide group enables chemoselective conjugation via copper-free or copper-catalyzed azide–alkyne cycloaddition (click chemistry) to attach the linker to an alkyne-bearing PROTAC fragment, allowing modular assembly under mild conditions. The carboxylic acid ends can be used for amide coupling or salt formation during PROTAC synthesis, supporting controlled attachment geometries and improved handling of the final construct. In targeted protein degradation research, this linker supports efficient, reproducible synthesis of multi-component degraders by providing a tunable distance and orientation between binding elements, which can be critical for achieving productive ternary complex formation and degradation potency.
Structure of 2093152-80-6
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N-(Azido-PEG4)-N-bis(PEG4-acid) is a polyethylene glycol (PEG)-based PROTAC linker designed to provide aqueous solubility, conformational flexibility, and a chemically addressable azide handle for modular assembly. Its PEG-rich architecture can help reduce steric constraints between targeting ligands and the recruited E3 ligase moiety, supporting efficient formation of productive ternary complexes. The azide functionality enables widely used conjugation strategies, and the terminal acid groups facilitate robust coupling to complementary building blocks. Detailed structural and reactivity considerations are provided below.
Structure: The linker comprises multiple PEG repeat units bearing an azide substituent and bis-carboxylic acid termini, connected through amide-forming nitrogen substitution. It contains ether linkages typical of PEG, an azide functional group for bioorthogonal chemistry, and carboxylic acids for salt formation and acyl coupling. Overall, it is highly polar and water-compatible.
Reactivity: The azide group is suitable for copper-catalyzed azide–alkyne cycloaddition or strain-promoted azide–alkene/alkyne conjugation, enabling selective attachment to complementary click partners under mild, ligand-preserving conditions. The carboxylic acids can be activated for amide bond formation using standard coupling reagents (e.g., carbodiimides with additives) in polar aprotic solvents. Mechanistically, click reactions proceed via cycloaddition, while acid coupling proceeds through an activated ester intermediate.
* 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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