Redox-based reagents for chemoselective methionine bioconjugation.
Science. 2017 Feb 10;355(6325):597-602
Authors: Lin S, Yang X, Jia S, Weeks AM, Hornsby M, Lee PS, Nichiporuk RV, Iavarone AT, Wells JA, Toste FD, Chang CJ
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 antibody-drug conjugates, and identification of hyperreactive methionine residues in whole proteomes.
PMID: 28183972 [PubMed – in process]