Azido-PEG9-acid

Azido-PEG9-acid is a polyethylene glycol-based PROTAC linker bearing a terminal azide and a carboxylic acid handle, enabling modular assembly of targeted protein degraders. Its PEG segment provides conformational flexibility and improved solubility, while the azide functionality supports bioorthogonal conjugation strategies commonly used in PROTAC workflows. The carboxylic acid facilitates coupling to targeting ligands or warheads, and the molecule will be described in detail below.

Structure: The linker consists of an azide-terminated PEG chain connected to a terminal carboxylic acid. It contains ether linkages within the PEG backbone, an organic azide for click-type reactivity, and a carboxylic acid for amide or ester formation. These features support aqueous compatibility and stable covalent conjugation.

Reactivity: The azide group is suited for copper-catalyzed azide–alkyne cycloaddition or related azide-based conjugation chemistries under conditions that preserve sensitive functional groups. The carboxylic acid can be activated for amide coupling using standard peptide-coupling reagents, typically in polar aprotic solvents with base. Mechanistically, covalent bond formation proceeds via click cycloaddition or acyl substitution after activation, enabling efficient PROTAC construction.