HO-PEG5-OH

This HO-PEG5-OH linker is a polyethylene glycol-based diol designed to serve as a flexible spacer in PROTAC architectures, helping to tune the effective distance and conformational freedom between the target-binding ligand and the E3 ligase recruiter. Its hydrophilic PEG character can improve solubility and reduce nonspecific interactions, supporting robust linker performance in targeted protein degradation workflows. Detailed structural and synthetic guidance is provided below.

Structure: HO-PEG5-OH is a PEG chain terminating in two hydroxyl groups, providing ether-rich connectivity and flexible rotatable bonds. The molecule contains repeating C–O ether linkages and terminal O–H functionalities, yielding a polar, hydrogen-bonding capable, water-compatible linker suitable for conjugation chemistry.

Reactivity: As a diol, it is commonly incorporated into PROTACs via hydroxyl-reactive coupling strategies such as formation of activated carbonate/ester intermediates or conversion to leaving-group derivatives followed by nucleophilic substitution with complementary electrophiles on ligands. Mild base-mediated esterification or carbamate-forming reactions are frequently used, with polar aprotic or aqueous-organic solvent systems to maintain solubility and control reactivity.