m-PEG3-NHS ester

m-PEG3-NHS ester is a polyethylene glycol (PEG)-based linker designed for efficient conjugation in PROTAC workflows, enabling controlled spatial separation between targeting ligands and E3-recruiting moieties. Its NHS-activated ester functionality supports rapid amide-bond formation under mild aqueous conditions, facilitating streamlined linker installation and improving synthetic flexibility. The detailed Structure and Reactivity characteristics are provided below for researchers planning targeted protein degradation constructs.

Structure: The linker comprises a PEG chain terminated with an N-hydroxysuccinimide ester, providing an activated carboxylate equivalent for nucleophilic acyl substitution. It contains ether linkages within the PEG backbone and an NHS leaving group, yielding a hydrophilic, flexible, and water-compatible conjugation handle.

Reactivity: The NHS ester reacts with primary amines to form stable amide bonds via acyl substitution, typically performed in buffered aqueous or mixed solvent systems at conditions that preserve NHS reactivity. Common nucleophiles include lysine-containing ligands or amine-functionalized intermediates. No special catalysts are required; reaction rates depend on pH and amine nucleophilicity, while NHS hydrolysis can compete, so fresh solutions and controlled residence time are important.