Issue 28, 2022

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


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.

Graphical abstract: Histidine-specific bioconjugation via visible-light-promoted thioacetal activation

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Article information

Article type
Edge Article
26 Apr 2022
25 Jun 2022
First published
27 Jun 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2022,13, 8289-8296

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

C. Wan, Y. Wang, C. Lian, Q. Chang, Y. An, J. Chen, J. Sun, Z. Hou, D. Yang, X. Guo, F. Yin, R. Wang and Z. Li, Chem. Sci., 2022, 13, 8289 DOI: 10.1039/D2SC02353A

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