Mal-PEG8-COOtBu

Mal-PEG8-COOtBu is a maleimide-terminated polyethylene glycol (PEG) linker designed for efficient conjugation chemistry in PROTAC workflows. Its maleimide handle enables selective coupling to thiol-containing ligands, while the PEG spacer supports favorable solubility and conformational flexibility for constructing targeted protein degraders. This product is particularly useful when assembling bifunctional molecules that require robust linkage between a warhead and an E3-recruiting element; the detailed structural and reactivity characteristics are described below.

Structure: The linker contains a maleimide moiety for thiol-reactive conjugation and a PEG chain that provides a flexible, hydrophilic scaffold. It also bears a protected carboxylate functionality (tert-butyl ester), incorporating an ester linkage that can be deprotected under standard conditions to reveal a carboxylic acid for further coupling.

Reactivity: The maleimide group typically undergoes Michael-type addition with primary thiols under mildly basic, aqueous or mixed-solvent conditions, often requiring careful control of pH and thiol stoichiometry to minimize side reactions. The tert-butyl ester can be converted to the free acid using acid-mediated deprotection, enabling subsequent amide or ester bond formation with activated carboxylic acid derivatives. Common coupling strategies include carbodiimide-mediated chemistry after deprotection.