Issue 26, 2016

Chemoselective modifications for the traceless ligation of thioamide-containing peptides and proteins

Abstract

Thioamides are single-atom substitutions of canonical amide bonds, and have been proven to be versatile and minimally perturbing probes in protein folding studies. Previously, our group showed that thioamides can be incorporated into proteins by native chemical ligation (NCL) with Cys as a ligation handle. In this study, we report the expansion of this strategy into non-Cys ligation sites, utilizing radical initiated desulfurization to “erase” the side chain thiol after ligation. The reaction exhibited high chemoselectivity against thioamides, which can be further enhanced with thioacetamide as a sacrificial scavenger. As a proof-of-concept example, we demonstrated the incorporation of a thioamide probe into a 56 amino acid protein, the B1 domain of Protein G (GB1). Finally, we showed that the method can be extended to β-thiol amino acid analogs and selenocysteine.

Graphical abstract: Chemoselective modifications for the traceless ligation of thioamide-containing peptides and proteins

Supplementary files

Article information

Article type
Paper
Submitted
11 May 2016
Accepted
26 May 2016
First published
06 Jun 2016

Org. Biomol. Chem., 2016,14, 6262-6269

Chemoselective modifications for the traceless ligation of thioamide-containing peptides and proteins

Y. J. Wang, D. M. Szantai-Kis and E. J. Petersson, Org. Biomol. Chem., 2016, 14, 6262 DOI: 10.1039/C6OB01020B

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