Electron-rich anilines as cleavable linkers for peptides

We report the development of a new electron-rich aniline (ERA)-based cleavable linker. Anilines can be incorporated into peptides during SPPS and are stable to most reaction conditions. ERA-containing peptides can be cleaved rapidly in the presence of oxidants, such as DDQ, CAN, and NaIO₄, in 30 min at room temperature. The compatibility of these conditions is demonstrated on peptides containing natural and unnatural amino acids. While the cleavages of other oxidatively labile linkers is known to cause decomposition of Tyr and Trp, these sensitive residues are stable to DDQ oxidations. An ERA-linker also enables the capture and release of a biotinylated peptide from immobilized streptavidin. ERA-linkers may serve as an excellent tool for peptide library screening applications.