N,N-Dimethylaminoxy Carbonyl, a Polar Protecting Group for Efficient Peptide Synthesis

Abstract

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Peptide coupling with minimal protection is one of the desired methods for the synthesis of peptides and proteins. To achieve regioselective amide bond formation, side chain protection is often essential; however, protecting groups potentially diminish peptide solubility and render the polar polyamide chain amphipathic due to their apolar nature. In this manuscript, we describe a new protecting group, N,N-dimethylaminoxy carbonyl (Dmaoc), and its use in peptide coupling reactions. The Dmaoc group has a relatively polar character compared to the Boc group, which is a conventional protecting group for the Nε-amine of Lys residues. This polar protecting group is removable by reduction in the buffer containing (±)-dithiothreitol (DTT). Furthermore, the Dmaoc group proved compatible with peptide ligation strategies featuring the activation of N-acyl diaminobenzamides (Dbz) with sodium nitrate to generate the respective benzotriazole leaving group. The Dmaoc/Dbz strategy described in this manuscript provides a new method for the chemical synthesis of peptides.

Keywords

• N,N-dimethylaminoxy carbonyl
• Dmaoc
• Dbz
• peptide coupling
• solid phase peptide synthesis
• chemical ligation