Expanding the versatility and scope of the oxime ligation: rapid bioconjugation to disulfide-rich peptides.

The oxime ligation is a valuable bioorthogonal conjugation reaction but with limited compatibility with disulfide-rich peptides/proteins and time-sensitive applications. Here we overcome these limitations by introducing a strategy that supports regiospecific control, oxidative folding, production of stable aminooxy-precursors for on-demand modification, and complete ligation within 5 min.