HO-PEG13-OH

This HO-PEG13-OH linker is a linear, hydrophilic polyethylene glycol diol designed to serve as a flexible spacer in PROTAC architectures. Its ether-rich backbone and terminal hydroxyl groups support modular conjugation to ligands, helping to tune solubility, conformational freedom, and effective reach between the target-binding and E3-recruiting components. The detailed structural and synthetic considerations for using this linker in PROTAC construction are provided below.

Structure: HO-PEG13-OH is a polyethylene glycol diol featuring repeating ether units that confer high polarity and flexibility. The molecule contains C–O ether linkages along the chain and terminal hydroxyl groups capable of forming hydrogen bonds. Overall, it behaves as a water-compatible, non-aromatic linker with a flexible, conformationally adaptable scaffold.

Reactivity: The terminal hydroxyl groups enable common PROTAC-compatible coupling strategies, including conversion to activated derivatives (for example, via esterification or carbonate formation) followed by nucleophilic substitution with complementary functional groups on ligands. Typical approaches use mild base or coupling reagents in organic solvents or solvent mixtures, with temperature control to preserve sensitive ligand motifs. The ether backbone is generally stable under standard ester/carbonate coupling conditions, supporting reliable linker installation.