m-PEG8-DBCO

m-PEG8-DBCO is a polyethylene glycol (PEG)-based bifunctional linker designed for modular PROTAC assembly and efficient conjugation workflows. The DBCO (dibenzocyclooctyne) handle enables highly selective strain-promoted azide–alkyne cycloaddition, supporting stable linkage formation under mild conditions. Its PEG spacer improves solubility and can reduce steric constraints between the recruited ligand modules, facilitating productive ternary complex formation. The detailed structure and reactivity considerations are provided below.

Structure: The linker comprises an m-substituted aromatic core bearing a DBCO cyclooctyne moiety connected to a PEG chain. It contains ether linkages within the PEG segment, an alkyne-containing strained ring system in DBCO, and aromatic carbon–carbon and carbon–hydrogen frameworks, yielding a flexible, hydrophilic scaffold.

Reactivity: DBCO reacts with azides via strain-promoted azide–alkyne cycloaddition (SPAAC), typically proceeding without copper catalysis. For PROTAC construction, azide-functionalized ligand or intermediate is combined with the DBCO linker under mild, aqueous-compatible conditions to form a stable triazole linkage. Commonly used solvents include buffered aqueous media or polar organic cosolvents, with temperature and pH chosen to preserve ligand integrity and minimize side reactions; no additional catalysts are required for SPAAC.