DSPE-PEG4-acid

DSPE-PEG4-acid is a PEG-based lipid linker designed to connect hydrophobic targeting ligands to PROTAC architectures while providing aqueous compatibility and conformational flexibility. Its amphiphilic character and terminal carboxylic acid enable robust conjugation strategies commonly used to tune solubility, linker length, and overall degrader performance. The detailed Structure and Reactivity parameters for building PROTAC constructs are provided below.

Structure: The linker combines a phospholipid-derived hydrophobic tail with an ethylene glycol–based PEG spacer and a terminal carboxylic acid. It contains ester and ether linkages within the PEG region, along with amide-compatible functional chemistry at the acid terminus. The resulting amphiphilic profile supports dispersion in aqueous media.

Reactivity: The terminal carboxylic acid can be activated for coupling to amine- or hydrazide-bearing handles on PROTAC components using standard acid-activation chemistries. Typical approaches rely on carbodiimide-mediated activation or related coupling reagents, often in polar aprotic solvents with base to promote amide-bond formation. Reaction conditions should be optimized to preserve sensitive ligands and minimize hydrolysis, following established PROTAC linker-conjugation practices.