The Bioorthogonal Isonitrile–Chlorooxime Ligation

Abstract

Bioorthogonal reactions are valuable tools for the selective labeling and imaging of natural products and proteins. Here, we present the reaction between isonitriles and chlorooximes as a ligation that proceeds quickly (<i>k</i> ≈ 1 M^-1 s^-1) and with high chemoselectivity in an aqueous environment. Imaging of metabolically labeled cell surface glycans underlined the tolerance of the ligation to common functional groups in cellular systems. Live-cell dual-labeling experiments revealed that the isonitrile-chlorooxime ligation is orthogonal to the strain-promoted azide-alkyne cycloaddition.