Biorthogonal tagging Staudinger ligations and related reactions - scope and applications in chemical biology
Juliana Ott1, Ute Schepers2, Stefan Bräse3
1Institute of Functional Interfaces, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.
Abstract:
The Staudinger ligation, first introduced by Bertozzi and co-workers based on the classical reaction described by Hermann Staudinger in 1919, represents a milestone in bioorthogonal chemistry. Exploiting the inert nature of organic azides and phosphines in biological systems, this reaction enables chemoselective ligation under physiological conditions without interfering with native biochemical processes. Its versatility has led to numerous applications, including labeling of glycans, DNA, and proteins, as well as the synthesis of glycopeptides and functional biopolymers. As the first reaction explicitly designed to be bioorthogonal, the Staudinger ligation set a benchmark for ligation strategies and continues to serve as a powerful tool for imaging, diagnostics, and peptide assembly. In this method paper, we describe the mechanisms and variants of the Staudinger ligation and provide detailed reaction protocols, experimental guidelines, and optimization strategies for its practical application in biological systems.
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