BDP FL-PEG4-TCO

BDP FL-PEG4-TCO is a polyethylene glycol-based PROTAC linker designed to connect targeting ligands while providing conformational flexibility and improved aqueous compatibility. Its functional handle enables efficient installation of trans-cyclooctene (TCO) moieties, supporting rapid, bioorthogonal capture with tetrazine-bearing partners during PROTAC assembly or downstream conjugation. The linker’s ether-rich scaffold and reactive TCO functionality make it well suited for constructing well-defined, modular degradation systems; detailed structural and reactivity considerations are provided below.

Structure: The linker comprises a PEG repeat unit architecture featuring ether linkages that confer hydrophilicity and chain flexibility. It contains a strained trans-cyclooctene (TCO) functional group and a conjugation-ready attachment point, supporting stable covalent linkage to other PROTAC components through standard organic coupling chemistry.

Reactivity: TCO-containing linkers participate in fast, strain-promoted inverse electron-demand Diels–Alder reactions with tetrazines under mild conditions. PROTAC assembly typically involves sequential covalent coupling of the linker to targeting ligands, followed by tetrazine-mediated ligation for rapid conjugation. Reactions are commonly performed in aqueous or mixed aqueous/organic solvents, with careful control to minimize premature TCO consumption; no special catalysts are required for the tetrazine–TCO cycloaddition.