Introducing Azomethine Imines to Chemical Biology: Bioorthogonal Reaction with Isonitriles
Athanasios Markos, Maurice Biedermann, Johannes Heimgärtner, Adeline Marie Schmitt, Kathrin Lang, Helma Wennemers
Abstract
Azomethine imines are valuable substrates for chemical synthesis in organic solvents that often require anhydrous conditions. Here, we introduce C, N -cyclic- N ′-acyl azomethine imines (AMIs) to bioorthogonal reactions in an aqueous environment. These AMIs are stable under physiological conditions and react rapidly ( k 2 = 0.1–250 M –1 s –1, depending on pH) and chemoselectively with isonitriles in the presence of biological nucleophiles, including thiols. Live-cell imaging of cell-surface-bound isonitriles underlines the biocompatibility of the AMI–isonitrile ligation, and simultaneous one-pot triple-protein labeling demonstrates its orthogonality to commonly used bioorthogonal reactions, such as the SPAAC and iEDDA ligations.