Azido-PEG5-NHS ester

Azido-PEG5-NHS ester is a bifunctional PEG-based linker designed for modular PROTAC assembly, enabling efficient conjugation of targeting ligands through NHS-ester chemistry while preserving a terminal azide handle for orthogonal coupling. Its flexible polyethylene glycol scaffold supports favorable solubility and linker mobility, which can improve productive ternary complex formation. The detailed Structure and Reactivity considerations are provided below to guide experimental design for PROTAC linker incorporation.

Structure: The linker contains a terminal azide for bioorthogonal click-type reactions and an N-hydroxysuccinimide ester for acyl transfer to nucleophiles. A PEG chain provides a flexible, hydrophilic spacer, with stable covalent amide/ester intermediates during coupling and an overall ether-rich backbone that enhances aqueous compatibility.

Reactivity: The NHS ester reacts with primary amines under mildly basic conditions to form stable amide bonds, typically using aqueous buffer systems compatible with protein or ligand conjugation. The azide enables copper-catalyzed or strain-promoted azide–alkyne cycloaddition strategies, depending on the coupling partner and compatibility requirements. Careful control of pH and moisture helps limit NHS hydrolysis; commonly used catalysts and solvents should be selected to maintain azide integrity and preserve ligand activity.