COOH-PEG4-COOtBu

This COOH-PEG4-COOtBu linker is a polyethylene glycol-based bifunctional module designed to connect ligands in targeted protein degradation (PROTAC) architectures. Its ether-rich, flexible scaffold supports productive spatial presentation of binding moieties while maintaining solubility and minimizing steric mismatch. The two terminal functional groups enable robust conjugation strategies commonly used to assemble PROTACs;

Structure: The linker contains a PEG chain featuring multiple ether linkages that impart conformational flexibility and favorable hydrophilicity. It bears a carboxylic acid terminus and a protected carboxyl group (tert-butyl ester), providing orthogonal functional handles for stepwise synthesis. The molecule is typically stable under standard coupling conditions.

Reactivity: The free carboxylic acid can participate in amide-bond formation via standard coupling chemistries, typically using carbodiimide-based activators with an auxiliary base in polar aprotic solvents. The tert-butyl ester can be selectively deprotected under acidic conditions to regenerate a second carboxylic acid for subsequent coupling. This orthogonal sequence supports modular PROTAC assembly through iterative ligand-linker conjugation, following established PROTAC linker synthesis principles.