Benzyl-PEG5-MS

Benzyl-PEG5-MS is a PEG-based linker designed for modular construction of PROTACs, enabling controlled spatial separation between a ligand and an E3-recruiting or substrate-binding moiety. Its PEG segment promotes favorable solubility and conformational flexibility, while the benzyl group and methanesulfonyl functionality support efficient synthetic attachment strategies. The linker is particularly useful when optimizing linker length, vector geometry, and overall degradation performance;

Structure: The molecule contains an ether-rich polyethylene glycol chain providing hydrophilicity and conformational flexibility. A benzyl substituent contributes an aromatic handle, while the methanesulfonyl group represents a sulfonyl leaving group. The structure is stabilized by C–O ether linkages and aromatic C–C bonds, supporting robust handling under standard organic synthesis conditions.

Reactivity: The methanesulfonyl functionality is suitable for nucleophilic substitution reactions commonly used in PROTAC assembly, where an appropriate nucleophile displaces the sulfonyl group to form a new C–N or C–O linkage. Typical conditions employ polar aprotic solvents and controlled base/temperature to balance reactivity and minimize side reactions. Reaction design should follow established linker–ligand coupling principles used for PROTAC synthesis, including purification of intermediates before final conjugation.