Redox-based reagents for chemoselective methionine bioconjugation

Cysteine can be specifically functionalized by a myriad of acid-base conjugation strategies for applications ranging from probing protein function to antibody-drug conjugates and proteomics. In contrast, selective ligation to the other sulfur-containing amino acid, methionine, has been precluded by its intrinsically weaker nucleophilicity. Here, we report a strategy for chemoselective methionine bioconjugation through redox reactivity, using oxaziridine-based reagents to achieve highly selective, rapid, and robust methionine labeling under a range of biocompatible reaction conditions. We highlight the broad utility of this conjugation method to enable precise addition of payloads to proteins, synthesis of…

• HH
  Howard Hughes Medical Institute

  Award: DE-AC02-05CH11231
• UD
  U.S. Department of Energy

  Awards: -AC02-05CH11231, 101528-002, 05CH11231, AC02-05CH11231, DE-AC02, DE-AC02-05CH11231, DE-AC02-
• HH
  Helen Hay Whitney Foundation
• NI
  National Institutes of Health

  Awards: 1S10OD020062-01, 1S10OD020062, GM79465, award296914, DE-AC02-05CH11231
• UO
  University of California, Davis
• LB
  Lawrence Berkeley National Laboratory

  Awards: DE-AC02-05CH11231, 05CH11231, 101528-002, AC02-05CH11231