Thiol-PEG8-alcohol

This Thiol-PEG8-alcohol linker is designed for modular PROTAC assembly, providing a PEG-based spacer with a terminal thiol handle for controlled conjugation to ligands or reactive intermediates. Its flexible, hydrophilic architecture can improve solubility and reduce steric bias at the ternary-complex interface, supporting efficient targeted protein degradation workflows. Detailed structural and reactivity guidance is provided below.

Structure: The linker consists of a polyethylene glycol chain terminating in an alcohol and a thiol functionality. It features ether linkages within the PEG backbone and a terminal thiol group capable of forming thioether or disulfide-derived connections. The overall structure is flexible and highly polar, promoting aqueous compatibility.

Reactivity: The terminal thiol enables conjugation via thiol–electrophile chemistry, including alkylation or coupling to activated carbonyl or halide/mesylate-type intermediates, typically under inert or thiol-stabilizing conditions. Disulfide exchange can be used when reversible linkages are desired. Solvents such as aqueous buffers with compatible co-solvents are commonly employed, and base or mild nucleophile activation is selected to preserve thiol integrity while driving selective bond formation.