Azido-PEG5-amine is a heterobifunctional polyethylene glycol linker bearing a terminal azide group and a primary amine at opposite ends. Structurally, it comprises a flexible PEG chain of moderate length that provides aqueous solubility, reduces nonspecific protein binding, and spaces conjugated moieties to enable productive ternary-complex formation in PROTAC systems. The azide handle is designed for bioorthogonal conjugation via copper-catalyzed or strain-promoted azide–alkyne cycloaddition, allowing attachment to an alkyne-functional warhead or targeting ligand, while the terminal amine can be used for amide coupling, reductive amination, or other nucleophilic derivatizations to install complementary reactive groups. In targeted protein degradation research, this linker facilitates modular synthesis of PROTACs by enabling orthogonal, stepwise assembly of binder and E3-recruiting elements, helping researchers tune linker length and flexibility to optimize degradation potency and selectivity while maintaining synthetic versatility.
Structure of 516493-93-9
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Azido-PEG5-amine is a polyethylene glycol (PEG)-based bifunctional linker designed for modular PROTAC synthesis, combining an azide handle for bioorthogonal conjugation with a terminal amine for coupling to warhead or E3 ligase ligands. Its PEG spacer improves solubility and can help tune linker flexibility and effective reach between binding motifs. The detailed structural and reactivity considerations for constructing PROTACs with this linker are provided below.
Structure: The linker contains an azide functional group and a primary amine separated by a PEG ether chain, providing a flexible, hydrophilic scaffold. It features ether linkages within the PEG backbone and terminal heteroatom-bearing functionalities suitable for orthogonal derivatization. Overall, it is typically handled as a stable, polar intermediate.
Reactivity: The azide group is well suited for copper-catalyzed azide–alkyne cycloaddition or related azide-based click conjugation strategies, enabling efficient attachment to alkyne-functional partners under standard click conditions. The terminal amine can participate in amide bond formation via activated carboxylic acids or coupling reagents, or in reductive amination where appropriate. Use commonly compatible polar solvents and mild bases; avoid strongly reducing or highly nucleophilic conditions that could compromise azide integrity.
* 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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