Bis-PEG25-NHS ester

Bis-PEG25-NHS ester, is a bifunctional polyethylene glycol (PEG)-based reagent designed for constructing PROTACs through NHS-ester chemistry. Its PEG architecture provides solubility and conformational flexibility, while the activated N-hydroxysuccinimide (NHS) ester groups enable efficient coupling to primary amines commonly present on ligands. The resulting conjugates are well-suited for assembling targeted protein degraders, and the detailed structural and reactivity characteristics are described below.

Structure: Bis-PEG25-NHS ester contains a PEG backbone bearing two NHS ester termini, connected through stable ether linkages. The NHS ester functionality provides an activated acyl group poised for nucleophilic substitution, while the PEG chain imparts hydrophilicity and flexible spacing between conjugated components.

Reactivity: The NHS esters react with primary amines via acyl substitution to form stable amide bonds, a widely used strategy for PROTAC linker installation. Coupling is typically performed in mildly basic aqueous buffers or mixed organic/aqueous systems to maintain amine nucleophilicity while limiting NHS hydrolysis. No special catalysts are generally required; careful control of pH, temperature, and stoichiometry helps drive selective conjugation and preserve linker integrity.