Mild and Chemoselective Peptide-Bond Cleavage of Peptides and Proteins at Azido Homoalanine

✍ Scribed by Jaap Willem Back; Olivier David; Gertjan Kramer; Géraldine Masson; Piotr T. Kasper; Leo J. de Koning; Luitzen de Jong; Jan H. van Maarseveen; Chris G. de Koster

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 249 KB
• Volume: 117
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/ange.200502431

✦ Synopsis

The chemical cleavage of amide (peptide) bonds usually requires harsh conditions. [1] As a result, side reactions and the lack of specificity of chemical amide-bond hydrolysis limits its scope in chemical biology and synthetic applications. Herein, we disclose our results on the selective cleavage of amide bonds in peptides and proteins that is milder than any previously reported chemical method.

The azide functional group is well suited for the in vivo labeling of biomolecules. [2] Azides combine a high chemical stability under physiological conditions with a unique reactivity that enables mild and selective organic transformations, such as the Staudinger ligation [3] and the azide-alkyne [3+2] cycloaddition. [4] Azido-functionalized amino acids [5] and azido sugars [4e] have been introduced into biomacromolecules and have subsequently been derivatized with specific labels to enable their detection, thereby demonstrating full bioorthogonality. [2] It has been shown that azido homoalanine (1) is effectively incorporated into proteins by the native methionyl tRNA synthetase of E. coli, thus allowing specific modification reactions. [5a] Azides, however, are susceptible to reduc-