Mal-amido-PEG24-CH2CH2COONHS ester

This Mal-amido-PEG24-CH2CH2COONHS ester is a bifunctional polyethylene glycol-based linker designed for efficient conjugation in PROTAC workflows. Its PEG spacer enhances solubility and can improve the effective reach and conformational flexibility between a targeting ligand and an E3 ligase binder. The NHS-ester handle enables straightforward, chemoselective coupling to primary amines, while the remaining functional groups support subsequent PROTAC assembly steps.

Structure: The linker comprises a PEG chain connected to a malonamide motif and a terminal ethyl spacer bearing an activated N-hydroxysuccinimide ester. It contains amide linkages, ether-rich PEG segments, and an NHS-activated carboxylate suitable for nucleophilic acyl substitution. Overall, it is typically water-compatible and chemically stable under controlled conditions.

Reactivity: The NHS ester is reactive toward primary amines via nucleophilic acyl substitution, forming a stable amide bond while releasing N-hydroxysuccinimide. For PROTAC synthesis, coupling is commonly performed under mildly basic aqueous or mixed solvent conditions that maintain NHS reactivity without promoting hydrolysis. Typical solvents include buffered aqueous media or polar aprotic mixtures; catalysts are generally not required. Reaction progress is monitored by analytical methods, and excess amine is used to drive completion before purification.