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Histidine-specific bioconjugation via visible-light-promoted thioacetal activation.

Chuan WanYuena WangChenshan LianQi ChangYuhao AnJiean ChenJinming SunZhanfeng HouDongyan YangXiaochun GuoFeng YinRui WangZigang Li
Published in: Chemical science (2022)
Histidine (His, H) undergoes various post-translational modifications (PTMs) and plays multiple roles in protein interactions and enzyme catalyzed reactions. However, compared with other amino acids such as Lys or Cys, His modification is much less explored. Herein we describe a novel visible-light-driven thioacetal activation reaction which enables facile modification on histidine residues. An efficient addition to histidine imidazole N3 under biocompatible conditions was achieved with an electrophilic thionium intermediate. This method allows chemo-selective modification on peptides and proteins with good conversions and efficient histidine-proteome profiling with cell lysates. 78 histidine containing proteins were for the first time found with significant enrichment, most functioning in metal accumulation in brain related diseases. This facile His modification method greatly expands the chemo-selective toolbox for histidine-targeted protein conjugation and helps to reveal histidine's role in protein functions.
Keyphrases
  • visible light
  • amino acid
  • photodynamic therapy
  • protein protein
  • binding protein
  • stem cells
  • drug delivery
  • room temperature
  • resting state
  • blood brain barrier
  • functional connectivity
  • rectal cancer