Zirconium-rich magnetic polyoxometalate-based metal–organic framework: Tailored for phosphopeptide analysis from lung cancer A549 cells

Polyoxometalate-based metal–organic frameworks (POMOFs) have emerged as a promising affinity material for separation and enrichment. In this work, zirconium-rich magnetic polyoxometalate-based metal–organic framework (Fe3O4@POMOF-Zr4+) was prepared and applied to selective enrichment of phosphopeptides. Fe3O4@POMOF-Zr4+ combined the advantages of metal–organic frameworks and polyoxometalate. By virtue of the strong binding affinity came from Fe–O clusters, V–O clusters, and rich zirconium ions, the novel affinity adsorbent was successfully applied to enrich phosphopetides from standard peptide mixtures. Fe3O4@POMOF-Zr4+ had good enrichment performance in non-fat milk, human saliva, serum, and lung cancer A549 cell lysate. [Display omitted] •V10O28-Zr4+ was filled into the pores of Fe3O4@MOF to construct magnetic POMOF.•Fe3O4@POMOF-Zr4+ combined the advantages of MOFs and POMs.•The material had high sensitivity, selectivity, and recovery for phosphopeptides.•The method showed high enrichment efficiency in A549 cell lysate. Polyoxometalate-based metal–organic frameworks (POMOFs) have become a promising affinity material for separation and enrichment. The analysis of protein phosphorylation represents a challenge for the development of efficient enrichment materials. Here, a novel zirconium-rich magnetic POMOF was successfully designed and prepared for the enrichment of phosphopeptides. The binding affinity of the nanomaterial partly came from Fe–O clusters in the MOF. The Lewis acid–base interactions between V–O clusters and zirconium ions in V10O28-Zr4+ and phosphate groups in phosphopeptides further strengthened the enrichment ability. The zirconium-rich magnetic POMOF was employed to capture phosphopeptides from non-fat milk, human saliva, and serum. Additionally, 748 unique phosphopeptide peaks were detected from the tryptic digests of lung cancer A549 cell proteins with a high specificity (86.9 %). POMOFs will become an active competitor for the design of protein affinity materials and will provide a new approach for phosphopeptide analysis.