Enabling identification of phosphorylated cysteine: Novel chemoselective synthetic and analytical methods
Protein phosphorylation plays a key role in the regulation of signaling pathways and many other cellular processes. Studies of phosphorylation have focused on serine, threonine and tyrosine amino-acid side chains, while the phosphorylation of other amino acids, such as phospho-histidine (pHis), -arginine (pArg), -lysine (pLys) and -cysteine (pCys), is less well understood. Studies have been hindered by technical limitations, primarily acid lability. To address this problem, Jordi Bertran-Vicente and colleagues have developed a novel chemoselective and stereochemically defined phosphorylation strategy for Cys residues. The method employs the nucleophilic reactivity of P(III)-reagents (phosphites) with electrophilic disulfides. The research team has also developed a mass spectrometry-based proteomic approach to identify and characterize pCys sites that naturally occur in peptides.