Sulfation, such as O-sulfation, is present in the eukaryotic proteome as a post-translational modification and is involved in the regulation of function; however, sulfation in proteins is not uniform, with various sulfopeptides and sulfoproteins existing in different sulfoforms. Delineating the precise role of sulfation in the function of peptides and proteins is, therefore, difficult and is made more complicated because of the lack of methods for controlling the presence and distribution of sulfation in the proteome. Now, Liu et al. have shown that fluorosulfate can be used as a latent precursor of sulfate in peptides and proteins.
Their method is based on the incorporation of a noncanonical amino acid containing the fluorosulfate moiety into the protein or peptide of interest. Normally, fluorosulfate is metabolically stable under physiological conditions; however, the team found that fluorosulfate can be converted to sulfate by hydroxamic acid reagents under physiologically relevant conditions that enable the creation of functional sulfopeptides. The team also developed a photocaged version of the hydroxamic acid to enable light-controlled unmasking of the reactive group and therefore both spatial control and temporal control of the sulfate group formation. Mechanistic studies revealed that the pathway for the conversion of fluorosulfate to sulfate is not through direct hydrolysis but instead resembles an unusual Lossen rearrangement. Notably, the team did not detect any side reactions with other amino acids.
This is a preview of subscription content, access via your institution