Azido-PEG4-propionic acid is a heterobifunctional PEG linker featuring a terminal azide group and a carboxylic acid at the opposite end, providing a short, flexible polyethylene glycol spacer of intermediate length. The azide handle enables copper-free or copper-catalyzed azide–alkyne cycloaddition (click chemistry) to covalently connect PROTAC components bearing complementary alkyne functionalities, while the terminal carboxyl group supports standard amide coupling or esterification to introduce the linker onto ligands such as E3 ligase binders or target-binding moieties. In PROTAC design, this linker architecture helps tune the effective distance and relative orientation between the recruited proteins, often improving ternary complex formation and thereby influencing degradation potency and selectivity. As a practical modular reagent, it facilitates rapid synthesis of degraders with controlled conjugation sites, supports parallel library generation, and allows systematic linker optimization in targeted protein degradation research.
Structure of 1257063-35-6
* For research and manufacturing use only. Not for human or clinical use.
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This Azido-PEG4-propionic acid linker is designed for modular assembly of PROTACs, providing a chemically addressable azide handle for reliable conjugation to targeting ligands and maintaining a flexible polyethylene glycol spacer that can improve effective reach and reduce steric constraints. Its propionic acid functionality enables straightforward coupling strategies, supporting efficient construction of degraders. The following points describe its structure and practical reactivity considerations in PROTAC synthesis in detail below.
Structure: The linker contains a terminal azide group and a carboxylic acid, connected through a polyethylene glycol segment that confers conformational flexibility. It features ether linkages within the PEG chain and an aliphatic propionic acid moiety, enabling solubility and stable covalent attachment via standard functional-group chemistry.
Reactivity: The azide group is well suited for bioorthogonal azide–alkyne cycloaddition or related azide conjugation approaches, typically requiring an alkyne partner under copper-free or copper-catalyzed conditions depending on substrate sensitivity. The carboxylic acid enables amide or ester formation via activation with coupling reagents, proceeding through acyl-activation and nucleophilic substitution. Common solvents include polar aprotic media, with reaction temperatures and pH tuned to preserve sensitive ligands.
* 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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