Labeling and Natural Post-Translational Modification of Peptides and Proteins via Chemoselective Pd-Catalyzed Prenylation of Cysteine

Thomas Schlatzer, Julia Kriegesmann, Hilmar Schröder, Melanie Trobe, Christian Lembacher-Fadum, Simone Santner, Alexander Kravchuk, Christian F. W. Becker, Rolf Breinbauer

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The prenylation of peptides and proteins is an important post-translational modification observed in vivo. We report that the Pd-catalyzed Tsuji–Trost allylation with a Pd/BIPHEPHOS catalyst system allows the allylation of Cys-containing peptides and proteins with complete chemoselectivity and high n/i regioselectivity. In contrast to recently established methods, which use non-native connections, the Pd-catalyzed prenylation produces the natural n-prenylthioether bond. In addition, a variety of biophysical probes such as affinity handles and fluorescent tags can be introduced into Cys-containing peptides and proteins. Furthermore, peptides containing two cysteine residues can be stapled or cyclized using homobifunctional allylic carbonate reagents.
Original languageEnglish
Pages (from-to)14931-14937
JournalJournal of the American Chemical Society
Volume141
Issue number37
DOIs
Publication statusPublished - 2019

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Prenylation
Post Translational Protein Processing
Labeling
Peptides
Cysteine
Allylation
Proteins
Protein Prenylation
Regioselectivity
Carbonates
Catalysts

Keywords

  • prenylation
  • bioconjugation
  • lipidation
  • peptide cyclization
  • stapled peptides

Fields of Expertise

  • Human- & Biotechnology

Cite this

Labeling and Natural Post-Translational Modification of Peptides and Proteins via Chemoselective Pd-Catalyzed Prenylation of Cysteine. / Schlatzer, Thomas; Kriegesmann, Julia ; Schröder, Hilmar; Trobe, Melanie; Lembacher-Fadum, Christian; Santner, Simone; Kravchuk, Alexander; Becker, Christian F. W. ; Breinbauer, Rolf.

In: Journal of the American Chemical Society, Vol. 141, No. 37, 2019, p. 14931-14937.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Schlatzer, Thomas

AU - Kriegesmann, Julia

AU - Schröder, Hilmar

AU - Trobe, Melanie

AU - Lembacher-Fadum, Christian

AU - Santner, Simone

AU - Kravchuk, Alexander

AU - Becker, Christian F. W.

AU - Breinbauer, Rolf

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AB - The prenylation of peptides and proteins is an important post-translational modification observed in vivo. We report that the Pd-catalyzed Tsuji–Trost allylation with a Pd/BIPHEPHOS catalyst system allows the allylation of Cys-containing peptides and proteins with complete chemoselectivity and high n/i regioselectivity. In contrast to recently established methods, which use non-native connections, the Pd-catalyzed prenylation produces the natural n-prenylthioether bond. In addition, a variety of biophysical probes such as affinity handles and fluorescent tags can be introduced into Cys-containing peptides and proteins. Furthermore, peptides containing two cysteine residues can be stapled or cyclized using homobifunctional allylic carbonate reagents.

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