Nontraceless Staudinger Ligation

By: Matthias Junkers, Aldrich ChemFiles 2008, 8.1, 7.

Aldrich ChemFiles 2008, 8.1, 7.

Bertozzi et al. pioneered the application of the Staudinger reaction as a ligation method for bioconjugates. In the course of their studies on the metabolic engineering of cell surfaces they designed a phosphine with an ester moiety as an intramolecular electrophilic trap. After formation of the iminophosphorane from the newly designed phosphine reagent and an azide, the ester moiety captures the aza-ylide in a fast intramolecular cyclization reaction before hydrolysis with water can occur. This process ultimately produces a stable amide bond.1

The phosphine reagent can be synthesized from aminoterephthalic acid methyl ester by diazotization, followed by iodination and subsequent Pd-catalyzed phosphinylation (Scheme 4). The free acid moiety allows the easy attachment of a wide choice of molecular probes to the phosphine reagent by standard esterification or amidation procedures. Thus, a fluorescence label or different detection probe can be linked to any biomolecule that has been equipped with an azide function by the Staudinger ligation even in living cells (Scheme 5). The following paragraph shows how GlycoProfile™ azido sugars can be incorporated into glycan structures in vivo, and be used to attach a FLAG® phosphine probe chemically.

Scheme 4(393673)(650064)

Scheme 5

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  1. Saxon, E.; Bertozzi, C.R. Science 2000, 287, 2007.

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