HO-PEG4-CH2-COOMe

This HO-PEG4-CH2-COOMe linker is a polyethylene glycol–based, hydroxyl-terminated spacer bearing a methyl ester for controlled conjugation in targeted protein degradation workflows. Its flexible, hydrophilic PEG segment supports productive ternary complex formation and can improve solubility and linker tolerance in PROTAC architectures. The methyl ester handle enables efficient synthetic diversification, and the hydroxyl functionality allows attachment to warheads or handles used in PROTAC synthesis;

Structure: The linker comprises a PEG chain with terminal hydroxyl functionality and an ester-bearing methylene connection. It contains ether linkages along the PEG backbone, an alkyl ester moiety, and a hydroxyl group capable of hydrogen bonding. Overall, it is flexible and polar, favoring aqueous compatibility and conformational adaptability.

Reactivity: The methyl ester group is suitable for ester-based coupling strategies and for downstream conversion to carboxylic acids under standard hydrolysis conditions, enabling amide or related bond formation. Typical PROTAC linker synthesis uses ester activation chemistry (e.g., carbodiimide-mediated routes after hydrolysis) or direct ester functionalization, often in polar organic solvents. The PEG hydroxyl can be functionalized via standard derivatization methods to install attachment points without disrupting the ether-rich backbone.