Synthesis of Insulin and Other Disulfide-rich Peptides Employing the 2-Nitroveratryl Moiety as a Photocleavable S-Protecting Group — ASN Events
  1. Schedule
  2. Session 3 SPPS Methodology II and Industrial Synthesis
  3. Synthesis of Insulin and Other Disulfide-rich Peptides Employing the 2-Nitroveratryl Moiety as a Photocleavable S-Protecting Group

Synthesis of Insulin and Other Disulfide-rich Peptides Employing the 2-Nitroveratryl Moiety as a Photocleavable S-Protecting Group (#11)

John Karas 1 2 3 4 , Denis Scanlon 5 , James Gardiner 3 , Frances Separovic 1 4 , Mohammed Akhter Hossain 2 , John Wade 2
  1. School of Chemistry, University of Melbourne, Parkville, Victoria, Australia
  2. Neuropeptides, Florey Neurosciences Institute, Parkville, Victoria, Australia
  3. Materials Science & Engineering, CSIRO, Clayton, Victoria, Australia
  4. Bio21 Institute, University of Melbourne, Parkville, Victoria, Australia
  5. School of Chemistry, University of Adelaide, Adelaide, South Australia, Australia

A novel, higher-yielding Fmoc/tBu-based solid-phase synthesis of human insulin is herein reported whereby the 2-nitroveratryl moiety is 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. The protecting group is incorporated into the peptide chain as a cysteine building block, and the photolysis reaction is first evaluated using the simpler model systems oxytocin which has one disulfide bond and α-conotoxin-ImI which has two. Both these syntheses were successful. Higher yields are reported for the insulin synthesis relative to previous methodologies. Both the α-conotoxin-ImI and insulin were tested in the relevant binding assays and were found to have the same affinity for their receptors as the positive control.