Rapid and Selective Chemical Editing of Ribosomally Synthesized and Post-Translationally Modified Peptides (RiPPs) via Cu^II -Catalyzed ?-Borylation of Dehydroamino Acids.

ABSTRACT: We report the fast and selective chemical editing of ribosomally synthesized and post-translationally modified peptides (RiPPs) by ?-borylation of dehydroalanine (Dha) residues. The thiopeptide thiostrepton was modified efficiently using Cu^II -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.

SUBMITTER: de Vries RH 

PROVIDER: S-EPMC7898795 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature