Staudinger ligation, peptide

Nilsson, B.L., Soellner, M.B., and Raines, R.T. (2003b) Protein Assembly Using the Staudinger Ligation. Peptide Revolution Genomics, Proteomics Therapeutics (M. Chorev, and T.K. Sawyer, eds.). American Peptide Society. 

Xu, J., DeGraw, A.J., Duckworth, B.P., Lenevich, S., Tann, C.-M., Henson, E.C., Gruber, S.J., Barany, G., and Distefano, M.D. (2006) Synthesis and reactivity of 6,7-dihydrogeranylazides reagents for primary azide incorporation into peptides and subsequent Staudinger ligation. Chem. Biol. Drug Des. 68, 85-96. 

The azide can also react with phosphine derivatives through the Staudinger ligation. Azidophenylalanine was incorporated into the Z-domain protein in E. coli or into peptides displayed on phage, and was labeled with fluorescein-derived phosphines in phosphate buffer at room temperature (Figure 9(b)). ... 

So far, the methods that have been shown to enable chemoselective peptide bond formation have relied upon the particular reactivity between thioesters and aminothiols. Almost simultaneously, Raines [36] and Bertozzi [37] reported a new method for the formation of a peptide bond with high chemoselectivity the so-called Staudinger ligation. This reaction had... 

Scheme 78 Staudinger Ligation Starting with Peptide-Derived Thioesters and AzidesI ...

A second approach relies on the traceless Staudinger ligation between an appropriately functionalized phosphine and an azide to produce a new amide bond [54]. This method has found extensive utility in the labeling of peptides and proteins [215]. Importantly, this method has also been used for the construction of native iV-linked glycans through the reaction between a glycosyl azide and a phosphine containing amino acid [216,217]. 

The Huisgen [3+2] cycloaddition between azides and alkynes is another bioorthognal ligation reaction for incorporation of probes into protein and peptide scaffolds. Two variants of this reaction have been developed using either copper(I) [218] or strained cyclooctyne molecules [219] to promote the reaction. As with the Staudinger ligation this method has found extensive use in protein and peptide labeling studies. 

Raines, Staudinger ligation a peptide from a thioester and azide, Org. Lett. 

B.L. Nilsson, L.L. Kiessling, R.T. Raines, High-yielding Staudinger ligation of a phosphinothioester and azide to form a peptide, Org. Lett. 2001, 3, 9. 

It is important to cite several other recently developed methods for peptide ligation, which include the traceless Staudinger ligations of Bertozzi [62], Raines [63], and their co-workers, the decarboxylative amide ligation (KAHA ligation) developed by Bode et al. [64], and the Ser/Thr ligation of Li et al. [65, 66]. While these methods can be considered complementary to NCL, they have various constraints which limit their general utility. 

Fig. 8 The head-to-tail macrocyclization of peptides through a traceless Staudinger ligation...

Hackenberger and Kleineweischede reported a traceless Staudinger ligation for the head-to-tail macrocyclization of peptides without a deprotection step (Fig. 8) [63]. In this strategy, a phosphine tethered to a thioester at the C-terminus of a peptide reacts intramolecularly with an azide at the N-terminus to form the cyclic peptide. 

Kleineweischede R, Hackenberger CPR (2008) Chemoselective peptide cyclization by traceless Staudinger ligation. Angew Chem Int Ed 47 5984-5988... 

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