m-PEG24-SH

m-PEG24-SH is a thiol-terminated polyethylene glycol linker designed for constructing PROTAC architectures that require efficient, flexible spacing between targeting and recruiting ligands. Its PEG-rich chain promotes solubility, reduces nonspecific interactions, and helps maintain productive ternary complex formation in targeted protein degradation workflows. The thiol handle enables straightforward conjugation strategies to assemble degraders, and the following sections describe the structure and practical reactivity considerations in detail.

Structure: m-PEG24-SH comprises a polyethylene glycol backbone terminated with a free thiol group. The linker features repeating ether linkages, providing high conformational flexibility and hydrophilicity, while the terminal sulfur enables thiol-specific coupling. These traits support stable, water-compatible conjugation environments for PROTAC synthesis.

Reactivity: The terminal thiol can be used for chemoselective coupling to electrophilic partners commonly employed in PROTAC assembly, including activated esters, maleimides, haloacetamides, or other thiol-reactive functional groups. Thiol conjugations are typically performed under inert or low-oxidation conditions to preserve thiol integrity, using aqueous or mixed organic solvents compatible with PEG linkers. Reaction progress is often monitored by analytical methods, and mild bases or buffering systems may be selected to control thiolate formation without damaging sensitive ligands.