Bis-PEG9-acid

Bis-PEG9-acid is a PEG-based bifunctional PROTAC linker designed to position two reactive handles with a flexible, hydrophilic spacer that can improve solubility and support productive ternary-complex formation. Its acid functionality enables robust coupling strategies to common warheads and ligands used in targeted protein degradation workflows. The detailed Structure and Reactivity parameters are provided below to guide experimental design and synthesis.

Structure: The linker comprises two PEG segments connected to terminal carboxylic acid groups, providing a long, flexible, ether-rich backbone. It contains multiple ether linkages and carboxylate-forming functionality, enabling hydrogen-bonding and favorable aqueous compatibility. The bifunctionality supports orthogonal or sequential conjugation to two partners.

Reactivity: Carboxylic acids are typically activated for amide or ester bond formation using standard coupling chemistries such as carbodiimide-based activation with additives that suppress side reactions. Suitable conditions generally involve polar aprotic or mixed aqueous media, controlled pH, and temperature optimization to preserve sensitive ligands. The mechanism proceeds via formation of an activated ester or acyl intermediate, followed by nucleophilic attack from an amine-bearing warhead or ligand to yield stable conjugates.