DBCO-PEG5-NHS ester

DBCO-PEG5-NHS ester is a bifunctional PROTAC linker designed to enable efficient conjugation between a strained-alkyne targeting handle and an amine-bearing protein or ligand via NHS-ester chemistry. Its PEG-based spacer improves aqueous solubility and helps reduce steric constraints during assembly, supporting reliable formation of well-defined conjugates used in targeted protein degradation workflows. The detailed Structure and Reactivity parameters are provided below.

Structure: The linker combines a cyclooctyne (DBCO) functionality with a polyethylene glycol spacer and a terminal N-hydroxysuccinimide ester. It contains an activated carboxylate for amide formation and an alkyne for strain-promoted azide–alkyne cycloaddition, with ether-rich PEG segments that confer flexibility and hydrophilicity.

Reactivity: The NHS ester reacts with primary amines under mild aqueous or mixed solvent conditions to form stable amide bonds, typically proceeding via nucleophilic acyl substitution. The DBCO group participates in strain-promoted azide–alkyne cycloaddition without added catalyst, using azide partners to drive rapid conjugation. Commonly, buffers compatible with amine coupling are selected, while azide-containing components are introduced under conditions that preserve protein/ligand integrity.