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

• Published in: Chemical science (Cambridge) Vol. 13; no. 28; pp. 8289 - 8296
• Main Authors: Wan, Chuan, Wang, Yuena, Lian, Chenshan, Chang, Qi, An, Yuhao, Chen, Jiean, Sun, Jinming, Hou, Zhanfeng, Yang, Dongyan, Guo, Xiaochun, Yin, Feng, Wang, Rui, Li, Zigang
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 20.07.2022; Royal Society of Chemistry; The Royal Society of Chemistry
• Subjects: Amino acids; Biocompatibility; Chemical reactions; Chemistry; Chemistry, Multidisciplinary; Conjugation; Histidine; Imidazole; Peptides; Physical Sciences; Proteins; Science & Technology; FUNCTIONALIZATION; SITE; PROTEIN; TYROSINE; PHOSPHOHISTIDINE; STRATEGY; CHEMISTRY; RESIDUES; PROXIMITY; RHODIUM CARBENOIDS
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d2sc02353a

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.