Login / Signup

Rapid and Selective Chemical Editing of Ribosomally Synthesized and Post-Translationally Modified Peptides (RiPPs) via CuII -Catalyzed β-Borylation of Dehydroamino Acids.

Reinder H de VriesJakob H VielOscar Paul KuipersGerard Roelfes
Published in: Angewandte Chemie (International ed. in English) (2020)
We report the fast and selective chemical editing of ribosomally synthesized and post-translationally modified peptides (RiPPs) by β-borylation of dehydroalanine (Dha) residues. The thiopeptide thiostrepton was modified efficiently using CuII -catalysis under mild conditions and 1D/2D NMR of the purified product showed site-selective borylation of the terminal Dha residues. Using similar conditions, the thiopeptide nosiheptide, lanthipeptide nisin Z, and protein SUMO_G98Dha were also modified efficiently. Borylated thiostrepton showed an up to 84-fold increase in water solubility, and minimum inhibitory concentration (MIC) assays showed that antimicrobial activity was maintained in thiostrepton and nosiheptide. The introduced boronic-acid functionalities were shown to be valuable handles for chemical mutagenesis and in a reversible click reaction with triols for the pH-controlled labeling of RiPPs.
Keyphrases
  • crispr cas
  • fatty acid
  • magnetic resonance
  • amino acid
  • high throughput
  • mass spectrometry
  • single cell
  • solid state
  • loop mediated isothermal amplification
  • visible light