Bis-PEG13-NHS ester

This Bis-PEG13-NHS ester is a bifunctional polyethylene glycol linker designed for efficient conjugation in PROTAC workflows, enabling the installation of amine-reactive handles on targeting ligands and/or E3 ligase binders. Its PEG architecture provides enhanced solubility and reduced nonspecific interactions, while the NHS ester functionality supports robust coupling under mild conditions. The following sections describe the linker’s structure and practical reactivity considerations in detail.

Structure: The molecule is a bis-functional PEG-based linker bearing N-hydroxysuccinimide ester groups at its termini. It contains ether-rich PEG segments that impart flexibility, hydrophilicity, and conformational mobility, with reactive acyl–oxygen bonds characteristic of NHS esters.

Reactivity: NHS esters react with primary amines to form stable amide linkages via nucleophilic acyl substitution. For PROTAC assembly, conjugate the linker to amine-containing ligands using mildly basic aqueous or mixed-solvent conditions, typically with buffers that maintain amine nucleophilicity while limiting hydrolysis. Avoid prolonged exposure to water and strong nucleophiles; no special catalysts are generally required, but careful control of pH and stoichiometry helps favor mono- or bis-conjugation as desired.