Mal-​PEG4-​propargyl

Mal-PEG4-propargyl is a bifunctional polyethylene glycol (PEG) linker designed for PROTAC assembly, enabling efficient conjugation between a targeting ligand and an E3 ligase binder while maintaining solubility and conformational flexibility. Its propargyl handle supports reliable click-type coupling strategies, and the PEG segment helps reduce aggregation and improve aqueous compatibility. The detailed Structure and Reactivity parameters are provided below.

Structure: The linker comprises a PEG chain terminated with a maleimide group and a propargyl (alkyne) moiety. It contains a maleimide double bond suitable for selective Michael-type addition and a terminal alkyne for bioorthogonal conjugation. The PEG segment confers hydrophilicity and flexible, ether-rich connectivity.

Reactivity: For PROTAC construction, the maleimide functionality is commonly engaged via nucleophilic thiol addition under mild aqueous conditions, forming stable thioether linkages. The propargyl alkyne can then be coupled to azide-bearing partners using copper-catalyzed or catalyst-free azide–alkyne cycloaddition, depending on compatibility with sensitive ligands. Typical setups use buffered aqueous media, with careful control of pH and thiol availability to drive selective coupling.