Sulfuric acid is the intermediate oxidation state of the amino acid cysteine ​​(Cys). Proteomics experiments have shown that this oxidation is an important post-translational modification in many proteins. In order to explore the structural and functional effects of the oxidation of Cys to sulfinic acid, a general method is needed to synthesize peptides containing Cys sulfinic acid.

Andrew Urmey and Neal Zondlo of the Department of Chemistry and Biochemistry at the University of Delaware reported on Peptide Science a new way to obtain such molecules.

It is now known that the oxidation of Cys to sulfinic acid can induce activation or inhibition of protein function changes, and many proteins will be enzymatically reduced by sulfinic acid. In addition, this post-translational modification is related to protein signaling. Therefore, the emerging importance of Cys sulfinic acid in stress response and other biological activities has recently come to the fore, and many studies are devoted to exploring its role.

Cys sulfinic acid-containing peptides have been synthesized before, but most of them have limitations. For example, low yields, multiple synthesis and purification steps, and/or competitive side reactions. Here, the author reports two methods, both involving the protection of the methoxybenzyl (Mob) group and the use of the commercially available Fmoc-Cys(Mob)-OH.

The first is to synthesize the sulfone of methoxybenzyl Fmoc-cysteine ​​and then incorporate it into the peptide using solid phase synthesis. The second involves the synthesis of peptides via the amide coupling of Fmoc-Cys(Mob)-OH, followed by the oxidation of peptide thioethers to sulfones using H2O2 in the presence of catalytic niobium carbide. In both cases, the peptide is then deprotected with 50% trifluoromethanesulfonic acid, 45% trifluoroacetic acid, and 5% water.

Due to the easy availability of Fmoc-Cys(Mob)-OH and the relatively common deprotection pathway, this method is very useful for studying the role of cysteine ​​sulfinic acid in stress response and other biological activities.

Research articles can be found in: AR Urmey, NJ Zondlo, Peptide Science, 2019, doi.org/10.1002/pep2.24137