m-PEG7-Ms

This m-PEG7-Ms linker is designed for constructing PROTACs by providing a polyethylene glycol spacer terminated with a methanesulfonate leaving group, enabling efficient conjugation to nucleophilic handles on targeting ligands. Its PEG-based architecture supports favorable solubility and conformational flexibility, which can improve productive ternary complex formation. The subsequent points describe its structure and practical reactivity considerations in PROTAC synthesis.

Structure: The linker contains an m-PEG7 polyethylene glycol chain bearing a mesylate (methanesulfonate) functional group. It features ether linkages within the PEG backbone and a sulfonate ester at the terminus, offering a stable scaffold with a reactive leaving group for substitution chemistry.

Reactivity: The mesylate terminus undergoes nucleophilic substitution under conditions commonly used for sulfonate ester activation in bioconjugation. Suitable nucleophiles include amines or other heteroatom-containing groups capable of attacking the activated carbon center, typically promoted by base in polar aprotic or mixed aqueous/organic solvents. Reaction proceeds via an SN-type substitution mechanism, and mild temperatures are often selected to preserve sensitive ligands during PROTAC assembly.