HO-PEG14-OH

HO-PEG14-OH is a polyethylene glycol-based bifunctional linker designed for constructing PROTACs and other targeted protein degradation conjugates. Its hydrophilic, flexible polyether scaffold can help tune solubility, reduce nonspecific interactions, and provide an adaptable spacing element between a ligand and an E3-recruiting module. The subsequent points describe its structural features and practical considerations for linkage chemistry in PROTAC synthesis.

Structure: HO-PEG14-OH is a PEG diol featuring terminal hydroxyl groups on a repeating ethylene oxide backbone. The structure contains ether linkages that confer conformational flexibility, hydrophilicity, and chemical stability under many standard organic synthesis conditions. Overall, it behaves as a water-compatible, flexible spacer.

Reactivity: As a diol, HO-PEG14-OH is commonly functionalized through standard alcohol-to-derivative transformations used in PROTAC linker assembly, such as conversion to activated carbonate, mesylate/tosylate, or other leaving-group intermediates, followed by nucleophilic substitution with complementary nucleophiles on protein-binding ligands. Typical protocols employ inert atmospheres, anhydrous polar solvents, and base or coupling reagents appropriate to the chosen activation chemistry.