Selective Modification of RiPPs via Diels-Alder Cycloadditions on Dehydroalanine Residues

Reinder de Vries, Jakob Viel, Ruben Oudshoorn, Oscar Kuipers, Gerard Roelfes*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)
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Abstract

We report the late stage chemical modification of ribosomally synthesized and posttranslationally modified peptides (RIPPs) by Diels-Alder cycloadditions to naturally occurring dehydroalanines. The tail region of the thiopeptide thiostrepton could be modified selectively and efficiently under microwave heating and transition metal free conditions. The Diels-Alder adducts were isolated and the different site- and endo/exo isomers were identified by 1D/2D 1H NMR. Via efficient modification of the thiopeptide nosiheptide and the lanthipeptide nisin Z the generality of the method was established. MIC assays of the purified thiostrepton Diels-Alder products against thiostrepton-susceptible strains displayed high activities comparable to that of native thiostrepton. These Diels-Alder products were also subjected successfully to Inverse-electron-demand Diels-Alder reactions with a variety of functionalized tetrazines, demonstrating the utility of this method for labeling of RiPPs.

Original languageEnglish
Pages (from-to)12698–12702
Number of pages5
JournalChemistry
Volume25
Issue number55
Early online date30-Jul-2019
DOIs
Publication statusPublished - 1-Oct-2019

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