2-nitroveratryl as a photocleavable thiol-protecting group for directed disulfide bond formation in the chemical synthesis of insulin

John Karas, Denis Scanlon, Briony Forbes, Irina Vetter, Richard Lewis, James Gardiner, Frances Separovic, John Wade, Mohammed Akhter Hossain

    Research output: Contribution to journalArticle

    23 Citations (Scopus)

    Abstract

    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).

    Original languageEnglish
    Pages (from-to)9549-9552
    Number of pages4
    JournalChemistry - A European Journal
    Volume20
    Issue number31
    DOIs
    Publication statusPublished - 28 Jul 2014

    Keywords

    • cysteine-protecting groups
    • insulin
    • peptides
    • photochemistry
    • regioselectivity

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