Redox-based reagents for chemoselective methionine bioconjugation

Targeting proteins at the other sulfur As the only amino acid with a thiol (SH) group, cysteine is easily targeted for site-selective protein modifications. Hydrophobic methionine also has sulfur in its side chain, but its capping methyl group has hindered analogous targeting efforts. Lin et al. introduce a complementary protocol to tether new substituents exclusively to methionine, even in the presence of cysteine. They used an oxaziridine group as an oxidant to form sulfimide (S=N) linkages. The approach allowed antibody-drug conjugation and chemoproteomic screening for reactive methionine surface residues. Science , this issue p. 597