Mal-PEG5-C2-NH2 hydrochloride

Mal-PEG5-C2-NH2 hydrochloride is a PEG-based bifunctional linker designed for constructing PROTACs via efficient conjugation to ligands and subsequent formation of ternary-protein degradation complexes. Its maleimide handle supports selective thioether formation with cysteine-containing partners, while the terminal amine enables complementary coupling strategies. The flexible polyethylene glycol segment helps modulate solubility and effective linker length, supporting robust synthesis and reliable performance in targeted protein degradation workflows. Detailed structural and reactivity considerations are provided below.

Structure: This linker contains a maleimide electrophile conjugated to a polyethylene glycol chain and a short spacer terminating in a primary amine as a hydrochloride salt. It features an activated alkene within the maleimide ring, ether linkages in the PEG backbone, and a protonated amine for improved handling and aqueous compatibility.

Reactivity: The maleimide group undergoes Michael-type addition with thiols to form stable thioether linkages under near-neutral aqueous conditions, typically using mild bases to promote thiol availability while minimizing maleimide hydrolysis. The terminal amine can be used for amide-bond or carbamate-forming couplings with activated carboxylic acids or carbonyl derivatives. Common approaches use standard peptide-coupling reagents and compatible solvents such as aqueous buffer with organic co-solvents, with careful control of pH and thiol stoichiometry to drive selective conjugation.