Thioamide Labeling of Proteins through a Combination of Semisynthetic Methods

Backbone thioamide substitutions in peptides and proteins provide a nearly isosteric substitution for their oxoamide counterparts with distinct spectroscopic and electrostatic properties that may be harnessed for biophysical studies. In this review, we discuss thiopeptide synthesis and the important advances made toward achieving thioamide replacements in larger, structurally defined proteins through native chemical ligation. Finally, we examine some of the protein systems that have been studied with thioamide substitutions to highlight their versatility and potential as biophysical probes.