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

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

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

8 Citaten (Scopus)
59 Downloads (Pure)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)12698–12702
Aantal pagina's5
TijdschriftChemistry
Volume25
Nummer van het tijdschrift55
Vroegere onlinedatum30-jul-2019
DOI's
StatusPublished - 1-okt-2019

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