CHO-Ph-CONH-PEG3-amine

CHO-Ph-CONH-PEG3-amine, is designed to connect a protein-binding ligand to an E3-recruiting module in PROTAC architectures. Its ether-rich PEG segment provides conformational flexibility and improved aqueous compatibility, while the aromatic and amide elements offer stable attachment points for controlled conjugation. These features can help tune linker length, reduce steric bias, and support efficient formation of ternary complexes.

Structure: The linker contains an ether-rich PEG chain for hydrophilicity and flexibility, flanked by an aromatic phenyl group and a carboxamide (CONH) linkage. It includes an amine terminus suitable for coupling, with stable C–N and C–O bonds and a resonance-stabilized aromatic ring.

Reactivity: The terminal amine enables PROTAC synthesis via standard amide-forming or carbamate-forming coupling strategies, typically using activated carboxylic acids or isocyanate/carbonyl-activated derivatives under mild base conditions. Common approaches employ coupling reagents compatible with PEGylated substrates, with polar aprotic solvents and controlled stoichiometry to minimize side reactions such as over-acylation.