NH-bis(PEG4-acid)
CAS No.: 2055041-59-1
Cat No.: BP-501208
4.5 
NH-bis(PEG4-acid) is a branched polyethylene glycol linker featuring a central secondary amine and two PEG4 arms terminated with carboxylic acid groups. Its extended, flexible PEG scaffold provides water solubility and conformational spacing that can reduce steric interference between the two ligands typically used in PROTAC constructs. In PROTAC design, the linker serves as a “molecular spacer” that positions an E3 ligase-recruiting moiety and a target-binding ligand at an appropriate distance and orientation to favor formation of a ternary complex and subsequent ubiquitination. The carboxylic acid functionalities enable robust conjugation strategies, such as amide coupling to activated ligand handles, allowing modular assembly and systematic tuning of linker length and hydrophilicity. This product is valuable for targeted protein degradation research because it supports reproducible linker synthesis, improves aqueous handling during synthesis and assays, and facilitates rational optimization of degradation potency and selectivity by varying attachment geometry.
Structure of 2055041-59-1
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This PROTAC linker, NH-bis(PEG4-acid), is designed to provide a hydrophilic, flexible connection between targeting and recruiting modules while maintaining chemical compatibility for amide-forming conjugation strategies. Its polyethylene glycol–based architecture supports favorable solubility and spatial presentation of functional groups, which can improve overall PROTAC assembly and performance in solution. The following sections describe its structure and practical reactivity considerations for constructing PROTACs in a research setting.
Structure: NH-bis(PEG4-acid) is a PEGylated, bis-functional linker featuring an amide-forming “acid” functionality and an amine-containing central motif. It contains repeating ether units that confer flexibility, polarity, and water compatibility, along with stable carbon–oxygen and carbon–nitrogen linkages suitable for conjugation chemistry.
Reactivity: This linker is typically used in PROTAC synthesis through acid-to-amine coupling to form amide bonds with appropriately functionalized ligands. Suitable approaches include carbodiimide-mediated coupling (often with an activating additive) under mild base conditions, commonly in polar aprotic solvents. The mechanism relies on activation of carboxylic acids followed by nucleophilic attack by an amine to yield robust, non-labile amide linkages that tolerate standard PROTAC handling.
* 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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