N-(Aminooxy-PEG2)-N-bis(PEG3-propargyl)

N-(Aminooxy-PEG2)-N-bis(PEG3-propargyl), is designed to enable modular assembly of targeted protein degraders by combining an aminooxy functional group with propargyl handles for orthogonal conjugation. Its PEG-rich architecture supports aqueous solubility and flexible spacing between binding and reactive motifs, which can improve effective proximity during ternary complex formation. The subsequent points describe its structure and practical reactivity for PROTAC construction in detail.

Structure: The linker contains an aminooxy group connected to a PEG spacer and two PEG3-propargyl arms on a central nitrogen. It features ether linkages within the PEG segments and terminal alkyne (propargyl) functionalities, providing a flexible, hydrophilic, and conformationally adaptable scaffold.

Reactivity: The propargyl termini support copper(I)-catalyzed azide–alkyne cycloaddition for attaching azide-bearing ligands or warheads, typically using Cu(I) sources and polar solvents under mild conditions. The aminooxy group can participate in oxime formation with aldehydes or ketones, enabling selective conjugation routes. Orthogonal compatibility with click chemistry supports stepwise PROTAC synthesis without cross-reactivity.