m-PEG5-2-methylacrylate

m-PEG5-2-methylacrylate is a polyethylene glycol (PEG)-based PROTAC linker building block designed to connect targeting ligands while providing solubility, conformational flexibility, and improved handling in aqueous and mixed organic systems. Its acrylate functionality enables efficient covalent incorporation into PROTAC constructs through well-established polymer- and bioconjugation-style chemistries. The linker’s ether-rich scaffold can help tune linker length and hydrophilicity to support productive ternary complex formation, and the following sections describe its structure and practical reactivity considerations in detail.

Structure: The linker comprises a PEG ether chain substituted with a 2-methylacrylate ester at the terminus. It contains multiple ether linkages, an activated α,β-unsaturated ester, and ester carbonyl functionality, providing a polar, flexible scaffold with a reactive electrophilic double bond.

Reactivity: The 2-methylacrylate group is suited for nucleophilic addition and Michael-type conjugations with thiols, amines, or other nucleophiles under mild, commonly used bioconjugation conditions. For PROTAC assembly, the linker is typically reacted with complementary functional groups on ligands or intermediates in appropriate buffering solvents, with base or catalyst selection guided by nucleophile type. Reaction progress is monitored by standard analytical methods to ensure controlled coupling and minimize side reactions.