Rapid and selective chemical editing of Ribosomally synthesized and Post-translationally modified Peptides (RiPPs) via Cu(II)-catalyzed β-borylation of dehydroamino acids

Reinder H de Vries, Jakob H Viel, Oscar P Kuipers, Gerard Roelfes*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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 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.

Original languageEnglish
Pages (from-to)3946-3950
Number of pages5
JournalAngewandte Chemie (International ed. in English)
Volume60
Issue number8
Early online date13-Nov-2020
DOIs
Publication statusPublished - 19-Feb-2021

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