Selenoimidazolium Salts as Supramolecular Reagents for Protein Alkylation

Chembiochem. 2020 Dec 11;21(24):3515-3520. doi: 10.1002/cbic.202000557. Epub 2020 Sep 18.


Se-benzyl selenoimidazolium salts are characterized by remarkable alkyl-transfer potential under physiological conditions. Structure-activity relationship studies show that selective monoalkylation of primary amines depends on supramolecular interactions between the selenoimidazole leaving group and the target nucleophile. We demonstrate that these reagents can be used for site-selective and nearly quantitative modification of the model protein lysozyme on Lys13, bypassing the higher intrinsic reactivities of Lys1 and Lys33. These observations introduce selenoimidazolium salts as novel class of electrophiles for selective N-alkylation of native proteins.

Keywords: ergothioneine; methyltransferase; protein alkylation; selenoimidazole; selenoneine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Imidazoles / chemistry*
  • Indicators and Reagents / chemistry*
  • Macromolecular Substances / chemistry
  • Models, Molecular
  • Molecular Structure
  • Muramidase / chemical synthesis*
  • Muramidase / chemistry
  • Muramidase / metabolism
  • Organoselenium Compounds / chemistry*
  • Salts


  • Imidazoles
  • Indicators and Reagents
  • Macromolecular Substances
  • Organoselenium Compounds
  • Salts
  • Muramidase