BrCH2CONH-PEG2-NHS ester

BrCH2CONH-PEG2-NHS ester, is designed for efficient conjugation in PROTAC workflows by providing a robust NHS-ester handle for amide-bond formation with lysine-containing ligands or engineered protein-binding moieties. Its ether-rich PEG segment improves aqueous solubility and can help preserve productive ternary complex formation by reducing steric constraints. The bromomethyl amide functionality further enables orthogonal coupling strategies.

Structure: The molecule combines a bromomethyl amide (BrCH2CONH) with an NHS ester for activated acyl transfer, linked through a short poly(ethylene glycol) chain. It contains amide and ester functionalities, multiple ether linkages, and a reactive N-hydroxysuccinimide leaving group, supporting water-compatible physicochemical behavior.

Reactivity: The NHS ester typically reacts with primary amines under mild, aqueous or mixed-solvent conditions to form stable amide bonds via nucleophilic acyl substitution, with the NHS group acting as the leaving moiety. Reaction efficiency depends on pH control to favor amine nucleophilicity while minimizing hydrolysis. The bromomethyl group can participate in alkylation or substitution reactions with suitable nucleophiles, enabling stepwise PROTAC linker assembly using orthogonal chemistries.