HO-PEG16-OH

This HO-PEG16-OH linker is a hydrophilic polyethylene glycol diol designed to provide flexible spacing between PROTAC-binding modules, improving solubility and enabling effective conjugation strategies. Its ether-rich backbone and terminal hydroxyl groups support robust linker functionalization while maintaining conformational adaptability in targeted protein degradation constructs. The detailed structure and reactivity considerations for building PROTACs are provided below.

Structure: HO-PEG16-OH consists of a poly(ethylene glycol) chain terminated by primary hydroxyl groups. The repeating ether units provide a flexible, hydrogen-bonding, water-compatible scaffold, with predominantly C–O ether linkages and terminal O–H functionalities that enable further derivatization.

Reactivity: The terminal alcohols are suitable for PROTAC assembly via standard hydroxyl-reactive chemistries such as esterification or ether/urethane formation, typically under dehydrating or activating conditions depending on the electrophile. Common approaches use activated carboxylic acids (e.g., acid chlorides or coupling-activated esters) or isocyanate/activated carbonate intermediates, with polar aprotic solvents and base catalysts to drive coupling while minimizing PEG backbone degradation.