Azido-PEG7-Br

Azido-PEG7-Br is a bifunctional polyethylene glycol linker designed for modular PROTAC assembly, combining an azide handle for chemoselective “click” conjugation with a bromide leaving group for subsequent functionalization. Its PEG-based scaffold provides conformational flexibility and improved solubility, which can help maintain productive ternary complex formation in targeted protein degradation workflows. The following sections describe the linker’s structure and its practical reactivity for constructing PROTACs in a stepwise, researcher-friendly manner.

Structure: Azido-PEG7-Br contains a PEG chain terminated by an azide and a bromide, enabling orthogonal coupling strategies. The azide group is a stable, bioorthogonal functional handle, while the bromide provides a reactive electrophilic site. The ether-rich PEG backbone confers hydrophilicity and conformational mobility.

Reactivity: For PROTAC construction, the azide terminus is commonly used in copper-catalyzed azide–alkyne cycloaddition with alkyne-bearing ligands under standard click conditions, yielding a stable triazole linkage. The bromide terminus can be exploited in nucleophilic substitution reactions with suitable nucleophiles to install additional functional groups. Typical approaches use inert atmosphere when needed, polar aprotic solvents, and catalysts such as copper(I) salts for click steps.