Mal-amido-PEG7-propionic acid

Mal-amido-PEG7-propionic acid is a polyethylene glycol-based PROTAC linker designed to connect a maleimide-reactive handle with a propionic-acid functionality, enabling modular assembly of targeted protein degraders. Its flexible PEG scaffold supports productive ternary complex formation by improving solubility and conformational adaptability, while the maleimide motif provides a widely used chemoselective conjugation strategy to cysteine-containing ligands. The detailed structural and reactivity considerations for PROTAC construction are provided below.

Structure: The linker comprises a PEG chain terminated with a maleimide amide and a propionic acid group, featuring an alkene-containing maleimide core and amide linkages along the backbone. Its ether-rich PEG segment imparts pronounced hydrophilicity and conformational flexibility, while the terminal carboxylic acid enables further coupling or functionalization.

Reactivity: Maleimide groups typically undergo Michael-type addition with thiols under mildly basic, aqueous conditions, favoring selective conjugation to cysteine residues. For PROTAC synthesis, the linker is commonly combined with thiol-functionalized targeting ligands while maintaining controlled pH to preserve maleimide reactivity and minimize side reactions such as hydrolysis. Subsequent steps can employ standard carboxylic-acid activation chemistry for amide or ester formation, using appropriate coupling reagents and compatible solvents.