m-PEG4-NH-DBCO

m-PEG4-NH-DBCO is a heterobifunctional PEG-based linker designed for constructing PROTACs and related targeted degradation conjugates via copper-free click chemistry. Its polyethylene glycol segment supports solubility and flexible spacing between binding elements, while the DBCO handle enables efficient conjugation to azide-functional ligands or building blocks. This combination facilitates modular assembly under mild conditions, helping researchers streamline synthesis of degraders; the following sections describe the structure and reactivity in detail.

Structure: The linker contains a methoxy-terminated PEG chain connected through an amide linkage to a cyclooctyne (DBCO) moiety. It features ether linkages within the PEG segment, an amide linkage, and a strained alkyne suitable for cycloaddition; no free terminal amine is present. Overall, it is typically water-compatible and conformationally flexible.

Reactivity: DBCO reacts selectively with azides through strain-promoted azide–alkyne cycloaddition under copper-free conditions. For PROTAC assembly, azide-bearing targeting ligands or intermediates are combined with the DBCO-functional linker in suitable polar solvents such as aqueous buffer or alcohol/water mixtures. The reaction proceeds via formation of a triazole linkage without requiring metal catalysts, and it is commonly performed at mild temperatures to preserve sensitive functional groups.