Rapid Photolysis-Mediated Folding of Disulfide-Rich Peptides

Nitin A. Patil, John A. Karas, John D. Wade, Mohammed Akhter Hossain, Julien Tailhades

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Structure–activity relationship studies are a highly time-consuming aspect of peptide-based drug development, particularly in the assembly of disulfide-rich peptides, which often requires multiple synthetic steps and purifications. Therefore, it is vital to develop rapid and efficient chemical methods to readily access the desired peptides. We have developed a photolysis-mediated “one-pot” strategy for regioselective disulfide bond formation. The new pairing system utilises two ortho-nitroveratryl protected cysteines to generate two disulfide bridges in less than one hour in good yield. This strategy was applied to the synthesis of complex disulfide-rich peptides such as Rho-conotoxin ρ-TIA and native human insulin.

Original languageEnglish
Pages (from-to)8599-8603
Number of pages5
JournalChemistry - A European Journal
Volume25
Issue number36
DOIs
Publication statusPublished - 26 Jun 2019

Keywords

  • disulfides
  • peptides
  • photolysis
  • protein engineering
  • protein folding
  • structure–activity relationships

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