N-(Boc-PEG5)-N-bis(PEG4-acid)

N-(Boc-PEG5)-N-bis(PEG4-acid) is a PEG-based PROTAC linker designed to provide controlled hydrophilicity, conformational flexibility, and efficient spatial separation between binding modules. Its protected amine functionality enables stepwise assembly, while the carboxy-terminated PEG segments support robust conjugation strategies commonly used in targeted protein degradation workflows. The following sections describe its structure and practical reactivity considerations for PROTAC synthesis in detail below.

Structure: This linker contains a Boc-protected nitrogen connected to a PEG5 chain, with two PEG4-acid arms attached to the same nitrogen. It features ether-rich PEG segments, amide/urethane-compatible connectivity, and terminal carboxylic acid groups, providing water-compatible, flexible, and polar characteristics.

Reactivity: The Boc group can be removed under standard acidolysis conditions to expose a reactive amine for subsequent coupling. The terminal carboxylic acids are suitable for amide-bond formation using activated carboxyl derivatives (for example, carbodiimide-based coupling with an amine partner) or alternative acyl-activation reagents. Reactions are typically performed in polar aprotic solvents with base to promote coupling efficiency, enabling modular PROTAC construction.