AUTHOR=Okamoto Ryo , Ono Emiko , Izumi Masayuki , Kajihara Yasuhiro 

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

JOURNAL=Frontiers in Chemistry

VOLUME=7

YEAR=2019

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2019.00173

DOI=10.3389/fchem.2019.00173

ISSN=2296-2646

ABSTRACT=<p>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, <italic>N,N</italic>-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 <italic>N</italic><sup>ε</sup>-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 <italic>N</italic>-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.</p>