2-Propenoic acid,2-[2-(2-hydroxyethoxy)ethoxy]ethyl ester

This PROTAC linker is designed to provide a flexible, hydrophilic connection motif that can be used to couple ligands while maintaining favorable solubility and minimizing steric disruption at the ternary-complex interface. Its ether-rich architecture and ester functionality support modular synthesis strategies commonly used in targeted protein degradation workflows. The detailed structural and synthetic considerations are provided below to guide experimental design and linker installation in PROTAC constructs.

Structure: The molecule is an acrylate-derived ester featuring a vinyl group and a poly(ethylene glycol)-like ether chain with terminal hydroxyl functionality. It contains ester and ether linkages, providing conformational flexibility and hydrogen-bonding capacity, which can influence solvation and ligand presentation in PROTAC assemblies.

Reactivity: The ester and alkene present complementary handles for PROTAC linker construction via established organic transformations, including nucleophilic acyl substitution or ester activation followed by coupling to ligand-bearing nucleophiles, as well as alkene-functionalization under standard radical or electrophilic addition conditions. Reaction planning should consider compatibility with alcohol/amine nucleophiles, typical ester-activation reagents, and polar solvents that support ether-chain solubility.