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A Fast and Quantitative Method for Post-translational Modification and Variant Enabled Mapping of Peptides to Genomes
Published on: May 22, 2018
Selective Modification of Ribosomally Synthesized and Post-Translationally Modified Peptides (RiPPs) through
Reinder H de Vries1, Jakob H Viel2, Ruben Oudshoorn1
1Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747, AG, Groningen, The Netherlands.
Abstract:
We report the late-stage chemical modification of ribosomally synthesized and post-translationally 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 1 H NMR. Via efficient modification of the thiopeptide nosiheptide and the lanthipeptide nisin Z the generality of the method was established. Minimum inhibitory concentration (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.
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