CHO-Ph-CONH-PEG6-acid

CHO-Ph-CONH-PEG6-acid, is designed to provide a chemically addressable connection between a target-binding ligand and an E3 ligase recruiter while maintaining favorable solubility and conformational flexibility. Its PEG-based spacer and amide-bearing architecture help support productive ternary complex formation by reducing steric constraints. The following sections describe key structural features and practical reactivity considerations for assembling PROTAC constructs using this linker.

Structure: The linker contains a phenyl core bearing an amide linkage and a terminal carboxylic acid, connected through a PEG chain that confers hydrophilicity and conformational flexibility. It features stable covalent bonds including aromatic C–C, carbonyl C=O, and amide C–N, supporting robust conjugation chemistry.

Reactivity: The terminal carboxylic acid enables coupling to amine- or hydrazide-functionalized partners via standard peptide/amide-forming strategies. Typical approaches use carboxyl activation (for example, carbodiimide-based reagents with an acid-activating additive) in polar aprotic solvents under controlled pH to promote amide bond formation. The PEG chain generally tolerates mild conditions, and reactions are commonly carried out to minimize hydrolysis and preserve linker integrity.