m-PEG11-SH

m-PEG11-SH is a thiol-terminated polyethylene glycol linker designed for modular assembly of PROTACs, enabling efficient conjugation between targeting ligands and E3-ligase recruiters. Its PEG-based, flexible scaffold helps tune solubility and linker length while maintaining chemical handle availability for controlled coupling. The thiol functionality supports robust attachment strategies commonly used in targeted protein degradation workflows; detailed structural and reactivity considerations are provided below.

Structure: The linker consists of a linear polyethylene glycol chain terminated by a terminal sulfhydryl group. It contains repeating ether linkages that confer flexibility and hydrophilicity, alongside a reactive thiol at the terminus. The ether-rich backbone promotes water compatibility, while the sulfur functionality provides a defined conjugation site for PROTAC construction.

Reactivity: The terminal thiol can participate in thiol–maleimide addition, thiol–disulfide exchange, or thiol-directed coupling schemes depending on the complementary functional group on the partner ligand. Typical PROTAC synthesis uses mild, aqueous or mixed-solvent conditions buffered to maintain thiol reactivity while minimizing oxidation. Reactions are often performed under inert atmosphere or with reducing conditions to limit disulfide formation, and purification commonly removes unreacted thiol and byproducts.