Chemical synthesis of peptides can allow the option of sequential formation of multiple cysteines through exploitation of judiciously chosen regioselective thiol-protecting groups. We report the use of 2-nitroveratryl (oNv) as a new orthogonal group that can be cleaved by photolysis under ambient conditions. In combination with complementary S-pyridinesulfenyl activation, disulfide bonds are formed rapidly in situ. The preparation of Fmoc-Cys(oNv)-OH is described together with its use for the solid-phase synthesis of complex cystine-rich peptides, such as insulin. Photochemistry: The 2-nitroveratryl moiety was employed as an orthogonal photocleavable thiol-protecting group for the directed synthesis of multiple disulfide bonds. A cysteine building block was prepared and found to be fully compatible with solid-phase peptide-synthesis protocols. This strategy was successfully applied to the synthesis of cystine-rich peptides such as α-conotoxin ImI and human insulin (see scheme).
- cysteine-protecting groups