2-Nitroveratryl as a Photo-cleavable Thiol Protecting Group for Directed Synthesis of Insulin and other Disulfide-rich Bioactive Peptides — ASN Events
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  3. 2-Nitroveratryl as a Photo-cleavable Thiol Protecting Group for Directed Synthesis of Insulin and other Disulfide-rich Bioactive Peptides

2-Nitroveratryl as a Photo-cleavable Thiol Protecting Group for Directed Synthesis of Insulin and other Disulfide-rich Bioactive Peptides (#42)

John A Karas 1 2 3 4 , Denis B Scanlon 5 , James Gardiner 2 , Briony Forbes 6 , Richard Lewis 7 , Irina Vetter 7 , Frances Separovic 3 4 , M. Akhter Hossain 1 , John Wade 1
  1. Florey Neurosciences, The University Of Melbourne, VIC, Australia
  2. Materials Science & Engineering, CSIRO, Clayton, Victoria, Australia
  3. School of Chemistry, University of Melbourne, Parkville, Victoria, Australia
  4. Bio21 Institute, University of Melbourne, Parkville, Victoria, Australia
  5. School of Chemistry, University of Adelaide, Adelaide, South Australia, Australia
  6. School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia
  7. Chemistry and Structural Biology Division, Institute for Molecular Bioscience, Brisbane, Queensland, Australia

Disulfide bonds play a critical role in maintaining the conformation and biological activity of cysteine-rich peptides, and many have a great deal of therapeutic potential. However, their synthesis presents many challenges, particularly when pursuing a regio-selective approach, which can often be low-yielding due to the necessary use of harsh reagents. The 2-nitroveratryl moiety was thus employed as a photocleavable thiol protecting group as part of a broader strategy to form each of the three disulfide bonds in a regioselective manner under ambient conditions. The protecting group was incorporated into the peptide chain as a cysteine building block, and the photolysis reaction first evaluated using simpler model systems such as oxytocin, which has one disulfide bond, and a-conotoxin-ImI which has two; both these syntheses were successful. Higher yields were reported for the native human insulin synthesis, relative to previous methodologies. Both a-conotoxin-ImI and insulin were tested in the relevant binding assays and were found to have the same activity as the positive control.