Chemoselektive Staudinger‐Phosphit‐Reaktion von Aziden für die Phosphorylierung von Proteinen

Abstract

Hohe Ausbeuten bei Raumtemperatur werden mit der Titelreaktion zur Modifizierung von Peptiden und Proteinen in einer Reihe von Lösungsmitteln, darunter Puffer bei physiologischem pH‐Wert, erzielt. In Kombination mit nichtnatürlicher Proteintranslation ermöglicht die Reaktion die ortsspezifische Einführung phosphorylierter Tyr‐Analoga in Proteine (siehe Schema).

Staudinger Ligation as a Method for Bioconjugation

“…Recently, Hackenberger and co-workers introduced the Staudinger-phosphite reaction for the chemoselective modification of proteins. [110] This reaction, first described by Kabachnik and Gilyarov, [111] is based on a modified Staudinger reaction, in which a phosphoramidate 93 is formed in a two-step process between a phosphite 92 and an azide 1 (Scheme 34). Having demonstrated the concept of the Staudinger-phosphite reaction, a chemoselective modification of azide-containing peptides and proteins was pursued (Scheme 35 a,b).…”

Azide: A Unique Dipole for Metal‐Free Bioorthogonal Ligations

“…Afterwards, the cells were treated (1 h) with a biotin‐labeled Staudinger probe, yielding fluorescent cells as determined by flow cytometry. The Staudinger ligation has also been applied for site‐specific introduction of phosphoramides as phosphate isosteres in proteins14 and for in vivo experiments, such as for cell‐surface remodeling,15 live‐cell imaging16 and the visualization of O‐linked glycosylation in mice 17. Further applications are not outlined here because the Staudinger ligation has been reviewed earlier 18…”

Charles Stark Draper Prize: F. H. Arnold / Heinz‐Maier‐Leibnitz‐Preis: C. P. R. Hackenberger / Franklin Institute Award: K. C. Nicolaou / Frontiers of Knowledge Award: G. A. Somorjai / Wilhelm‐Manchot‐Forschungsprofessur: H. Waldmann

“…Seine Forschungsinteressen liegen in der Entwicklung chemoselektiver Ligationsstrategien und der Synthese modifizierter Peptide und Proteine. [2] Hackenberger er- …”