Bis-PEG10-NHS ester

This Bis-PEG10-NHS ester is a bifunctional polyethylene glycol (PEG) linker designed for efficient conjugation in targeted protein degradation workflows. Its NHS-ester chemistry enables rapid coupling to primary amines on ligands, facilitating the assembly of PROTAC architectures with improved solubility and reduced nonspecific interactions. The linker’s dual reactive ends support modular synthesis, and the following sections describe its structure and practical reactivity considerations in detail.

Structure: The molecule is a PEG-based bis-functional linker bearing two N-hydroxysuccinimide (NHS) ester groups. It contains stable amide-forming electrophiles connected through flexible ethylene glycol units, providing a hydrophilic, conformationally mobile scaffold suitable for bioconjugation and linker-mediated spacing.

Reactivity: NHS esters react with primary amines to form stable amide bonds via nucleophilic acyl substitution. For PROTAC linker construction, coupling is typically performed under mildly basic, aqueous or mixed solvent conditions that maintain amine nucleophilicity while preserving NHS ester reactivity. Commonly used solvents include buffered water or alcohol-containing buffers, with temperature and pH optimized to balance conversion and hydrolysis. No specific catalyst is required; careful control of stoichiometry and timing helps limit side reactions from NHS ester hydrolysis.