NH-bis-PEG5

NH-bis-PEG5 is a polyethylene glycol (PEG)-based bifunctional linker designed to connect an E3 ligase ligand and a target-binding warhead in PROTAC constructs. Its PEG-rich architecture provides conformational flexibility and improved solubility, supporting efficient formation of productive ternary complexes. The linker’s two reactive termini enable modular synthesis of PROTACs, and the resulting conjugates can be optimized for linker length, polarity, and spatial presentation. Detailed structural and synthetic guidance is provided below.

Structure: NH-bis-PEG5 is a bis-PEG linker featuring an amine-containing “NH” functional group at each end and a PEG chain segment that offers ether-rich, flexible connectivity. The scaffold contains multiple ether linkages, characteristic C–N and C–O bonds, and exhibits hydrophilic, water-compatible behavior typical of PEG materials.

Reactivity: Suitable PROTAC assembly typically relies on end-group chemistries that form stable amide, urea, or related linkages between the linker termini and complementary functional groups on ligands. Common approaches include coupling reactions using activated carboxylic acids or isocyanate/activated amine intermediates, often employing standard peptide-coupling reagents and base in polar aprotic solvents. Reaction conditions should be optimized to preserve ligand integrity and minimize PEG oxidation or hydrolysis.