Phosphopeptide Enrichment Methods

Phosphorylation is the covalent attachment of phosphate group to the structure which is one of the most common post- translational modification on cellular proteins. Mass spectrometry is used as the most efficient technique for characterizing phosphoproteins taking charge in cellular processes. However, phoshopeptides have low ionization efficiency which is a very important parameter for mass spectrometry. Furthermore, the concentration of phosphopeptides is usually lower than the detection limit of mass spectrometric techniques because of the substoichiometric phosphorylation. Enrichment studies, which is the selective separation of phosphopeptides from the respective environment for concentrating them before mass spectrometric analysis, are performed for solving these problems.

Atakay, M., Çelikbıçak, O.,  Salih, B. (2012), Analytical chemistry, 84(6), 2713-2720.

Phosphopeptides bind to chelating metal ions through metal-phosphate ion-pair interactions in immobilized metal ion affinity chromatography (IMAC). Metal oxide affinity chromatography (MOAC; for example, TiO2, ZrO2) is also used to enrich phosphopeptides onto surfaces based on bidentate interactions between metal oxides and phosphate groups. Ion exchange resins also allow for the enrichment of phosphopeptides on the basis of the charges of the species. Phosphate groups are acidic in nature in phosphopeptides, owing to the negative charges on them. Therefore, strong anion exchange (SAX) chromatography is also convenient for phosphopeptide enrichment.