Ms-PEG3-CH2CH2COOH

This Ms-PEG3-CH2CH2COOH linker is designed for constructing PROTACs that require a stable, water-compatible spacer terminating in a carboxylic acid handle. Its polyethylene glycol segment supports solubility and can help tune the effective distance and flexibility between the target-binding ligand and the E3 ligase-recruiting moiety. The carboxylate functionality enables straightforward conjugation strategies, and the methanesulfonyl (Ms) leaving group supports efficient linker attachment in PROTAC workflows. Detailed structural and reactivity considerations are provided below.

Structure: Ms-PEG3-CH2CH2COOH comprises a PEG-based flexible chain bearing a terminal carboxylic acid and a methanesulfonyl-activated group. It contains ether linkages characteristic of PEG, an alkyl spacer, and a carboxylic acid that can form salts. The overall polarity supports aqueous handling and conjugation compatibility.

Reactivity: The methanesulfonyl-activated functionality is suitable for substitution reactions with nucleophiles commonly used in PROTAC assembly, following principles of leaving-group-driven displacement. Carboxylic acid termination can be converted to activated ester or coupling intermediates under standard peptide-coupling or carboxyl-activation conditions, enabling amide or related bond formation. Typical approaches use polar aprotic solvents and base/acid activation systems appropriate to the chosen nucleophile and coupling chemistry.