Cysteine-Selective Modification of Peptides and Proteins via Desulfurative C−C Bond Formation

Rhys C. Griffiths, Frances R. Smith, Diyuan Li, Jasmine Wyatt, David M. Rogers, Jed E. Long, Lola M.L. Cusin, Patrick J. Tighe, Robert Layfield, Jonathan D. Hirst, Manuel M. Müller, Nicholas J. Mitchell*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

The site-selective modification of peptides and proteins facilitates the preparation of targeted therapeutic agents and tools to interrogate biochemical pathways. Among the numerous bioconjugation techniques developed to install groups of interest, those that generate C(sp3)−C(sp3) bonds are significantly underrepresented despite affording proteolytically stable, biogenic linkages. Herein, a visible-light-mediated reaction is described that enables the site-selective modification of peptides and proteins via desulfurative C(sp3)−C(sp3) bond formation. The reaction is rapid and high yielding in peptide systems, with comparable translation to proteins. Using this chemistry, a range of moieties is installed into model systems and an effective PTM-mimic is successfully integrated into a recombinantly expressed histone.

Original languageEnglish
Article numbere202202503
JournalChemistry - A European Journal
Volume29
Issue number16
DOIs
Publication statusPublished - 16 Mar 2023

Keywords

  • bioconjugation
  • cysteine
  • desulfurization
  • post-translational modifications
  • site-selective

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