Azido-PEG15-t-butyl ester

Azido-PEG15-t-butyl ester is a PEG-based, azide-functional linker designed for modular construction of PROTACs and other targeted degradation scaffolds. Its flexible polyethylene glycol segment supports productive ternary complex formation, while the azide handle enables bioorthogonal conjugation to ligands under mild conditions. The tert-butyl ester provides a chemically addressable functional group for downstream derivatization and controlled stability during synthesis. The following points describe its structure and practical reactivity for linker installation in PROTAC workflows.

Structure: This linker contains a polyethylene glycol chain providing conformational flexibility and hydrophilicity, capped by a tert-butyl ester moiety and an azide functional group. It features ether linkages along the PEG backbone and ester connectivity at the terminal group, enabling stable storage and selective chemical transformations.

Reactivity: The azide group is suitable for copper-free or copper-catalyzed azide–alkyne cycloaddition, enabling efficient attachment of complementary alkyne-bearing ligands. The tert-butyl ester can be cleaved under acid-promoted conditions to reveal a carboxylic acid for amide coupling to targeting ligands. Typical PROTAC synthesis uses inert atmospheres when needed, with polar organic solvents for ester handling and standard peptide-coupling reagents for final bond formation.