Azido-PEG4-amido-tri-(carboxyethoxymethyl)-methane
CAS No.: 1398044-51-3
Cat No.: BP-501216
Purity: 96%
4.5 
Azido-PEG4-amido-tri-(carboxyethoxymethyl)-methane is a heterobifunctional PEG-based PROTAC linker featuring a terminal azide handle for bioorthogonal conjugation and an amide-linked PEG4 spacer that provides aqueous solubility and conformational flexibility. The tri-(carboxyethoxymethyl)-methane motif introduces multiple carboxylate-bearing substituents, enabling controlled attachment chemistry and enhancing hydrophilicity, which can improve the handling and presentation of the degrader construct in cellular assays. In PROTAC design, this scaffold functions as a spacer and coupling element that connects a ligand-bearing partner to another molecular component via click-type azide reactivity, while the PEG segment helps maintain productive geometry for ternary complex formation between the target protein and the E3 ligase recruiter. Its modular, solubilizing architecture makes it valuable for systematic linker optimization, including studies of how linker length, polarity, and flexibility influence degradation potency and selectivity.
Structure of 1398044-51-3
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This Azido-PEG4-amido-tri-(carboxyethoxymethyl)-methane linker is designed for modular synthesis of PROTACs, combining a bioorthogonal azide handle with a polyethylene glycol spacer and multiple carboxylate-bearing termini. Its flexible, hydrophilic architecture can improve solubility and reduce steric constraints between binding elements, supporting efficient formation of ternary complexes. Detailed structural and reactivity considerations for PROTAC assembly are provided below.
Structure: The linker incorporates an azide functional group, an amide linkage, and a PEG-derived flexible spacer, connected to a tri-functional methane core bearing carboxyethoxymethyl substituents. It contains multiple ester-like ether segments and carboxylate-bearing termini, enabling water-compatible, polar behavior and robust conjugation chemistry.
Reactivity: The azide moiety supports copper-catalyzed or strain-promoted azide–alkyne cycloaddition for installing PROTAC warheads under mild conditions, typically using appropriate ligands and oxygen-tolerant setups when required. The amide and carboxylate-bearing groups enable coupling to targeting ligands via standard amide-forming strategies, commonly employing carbodiimide-based activation in polar organic solvents with controlled pH to favor selective bond formation.
* 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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