Protecting Group Variations of Delta-mercaptolysine Useful in Chemical Ubiquitylation

The high efficiency and chemoselectivity of peptide ubiquitylation that is achieved using the delta-mercaptolysine prompted us to expand the scope of this residue in various ligation schemes. In this report, we demonstrate the synthesis of five analogues of this important amino acid bearing a variety of protecting groups, which is essential in sequential peptide ligation and ubiquitylation. The key-step in the synthesis is the nucleophilic 1,4-addition of a variety of thiols on a nitro olefin scaffold.