Azido-PEG12-propargyl

Azido-PEG12-propargyl is a bifunctional polyethylene glycol (PEG) linker designed for modular PROTAC assembly, enabling orthogonal conjugation through azide and terminal alkyne (propargyl) handles. Its flexible, hydrophilic PEG scaffold can improve solubility and provide an adaptable spatial linker length between ligands, supporting efficient formation of targeted protein-degrading constructs. The points below describe the structure and practical reactivity considerations in detail.

Structure: The linker contains a PEG chain bearing an azide group and a propargyl (terminal alkyne) substituent. It features ether linkages within the PEG backbone, plus carbon–carbon and carbon–nitrogen functionalities at the reactive termini, giving a flexible, polar, and conformationally mobile scaffold.

Reactivity: The azide and terminal alkyne enable copper-catalyzed azide–alkyne cycloaddition for “click” conjugation, typically using Cu(I) generated in situ from copper salts with a reducing system and a stabilizing ligand. Alternatively, strain-promoted azide–alkyne cycloaddition can be used when copper-free conditions are preferred. Reactions are commonly performed in polar organic/aqueous mixtures under conditions that preserve sensitive biomolecule conjugates.