Selenolysine: A New Tool for Traceless Isopeptide Bond Formation

Rebecca Notis Dardashti, Shailesh Kumar, Shawn M. Sternisha, Post Sai Reddy, Brian G. Miller, Norman Metanis

Research output: Contribution to journalArticlepeer-review


Despite their biological importance, post-translationally modified proteins are notoriously difficult to produce in a homogeneous fashion by using conventional expression systems. Chemical protein synthesis or semisynthesis offers a solution to this problem; however, traditional strategies often rely on sulfur-based chemistry that is incompatible with the presence of any cysteine residues in the target protein. To overcome these limitations, we present the design and synthesis of γ-selenolysine, a selenol-containing form of the commonly modified proteinogenic amino acid, lysine. The utility of γ-selenolysine is demonstrated with the traceless ligation of the small ubiquitin-like modifier protein, SUMO-1, to a peptide segment of human glucokinase. The resulting polypeptide is poised for native chemical ligation and chemoselective deselenization in the presence of unprotected cysteine residues. Selenolysine's straightforward synthesis and incorporation into synthetic peptides marks it as a universal handle for conjugating any ubiquitin-like modifying protein to its target.

Original languageAmerican English
Pages (from-to)4952-4957
Number of pages6
JournalChemistry - A European Journal
Issue number22
StatePublished - 16 Apr 2020


  • SUMOylation
  • chemical protein synthesis
  • deselenization
  • expressed protein ligation
  • post-translational modification

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Organic Chemistry


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