Thiol-C10-amide-PEG8

Thiols are widely used in PROTAC linker chemistry to enable efficient, modular assembly of bifunctional degraders that couple a targeting ligand to an E3 ligase binder. Thiol-C10-amide-PEG8 provides a PEG-based, amide-containing tether designed to promote solubility and conformational flexibility, while retaining a reactive thiol handle for subsequent conjugation. The molecule is therefore well suited for constructing PROTACs where controlled linker length and functional-group compatibility are critical;

Structure: The linker features an aliphatic decyl segment connected through an amide linkage to a polyethylene glycol chain, terminating in a thiol functionality. It contains C–C and C–N/C–O amide-related bonds, ether linkages within the PEG domain, and a sulfur–hydrogen group suitable for controlled derivatization.

Reactivity: The terminal thiol can be used for thiol–maleimide or thiol–disulfide exchange strategies, enabling conjugation to complementary electrophiles under mild, aqueous-compatible conditions. Typically, thiol-reactive PROTAC assembly is performed with appropriate buffering to maintain thiol availability, using inert atmosphere or reducing conditions when disulfide intermediates are involved. Solvents such as aqueous mixtures with organic co-solvents are commonly selected to balance solubility and reaction kinetics, with temperature and pH tuned to preserve linker integrity and coupling efficiency.