Bis-PEG21-NHS ester

Bis-PEG21-NHS ester, is designed to enable efficient conjugation of two amine-bearing ligands through NHS-ester chemistry, supporting the assembly of bifunctional degraders. Its PEG-based architecture provides a hydrophilic, flexible spacer that can improve solubility and help tune effective intramolecular positioning between the target-binding and E3-recruiting modules. The detailed structural and reactivity characteristics are provided below.

Structure: Bis-PEG21-NHS ester contains a PEG-based, flexible linker bearing two N-hydroxysuccinimide (NHS) ester functional groups. The molecule features amide-forming reactive acyl–oxygen bonds and ether linkages within the PEG chain, promoting hydrophilicity and conformational mobility relevant to PROTAC geometry.

Reactivity: The NHS esters react with primary amines to form stable amide bonds via nucleophilic acyl substitution. Suitable coupling is typically performed under mildly basic conditions to activate amine nucleophilicity while preserving NHS ester integrity. Common approaches use aqueous or mixed aqueous organic solvents, with careful control of pH and avoidance of competing nucleophiles such as primary amine-containing buffers. Catalysts are generally unnecessary; the process relies on the intrinsic electrophilicity of NHS esters.