Magnetic Binary Metal-Organic Framework As a Novel Affinity Probe for Highly Selective Capture of Endogenous Phosphopeptides

Highly efficient detection of endogenous phosphopeptides from complex biosamples is essential in phosphopeptidomics analysis due to the severe disturbance caused by the chaotic biological environment. In this study, for highly selective capture of endogenous phosphopeptides, a magnetic binary metal-organic framework (MOF) with Zr-O and Ti-O centers (denoted as Fe3O4@PDA@Zr-Ti-MOF) was designed and synthesized by a facile postsynthetic method. Briefly, Zr-based MOF was first coated on the surface of magnetic Fe3O4 with polydopamine (PDA) as a linker, and then, the as-prepared Fe3O4@PDA@Zr-MOF was exposed to DMF solution containing TiCl4(THF)(2), resulting in the successful synthesis of Fe3O4@PDA@Zr-Ti-MOF. This newly prepared Fe3O4@PDA@Zr-Ti-MOF owned the merits of large specific surface area, unique porous structure, and superparamagnetism as well as the enhanced dual affinities of Zr-O and Ti-O centers toward both endogenous mono-phospho-peptides and multiphospho-peptides, showing highly improved performance with better selectivity and sensitivity compared to single-metal centered MOFs (Fe3O4@PDA@Zr-MOF, Fe3O4@PDA@Ti-MOF). The Fe3O4@PDA@Zr-Ti-MOF was also successfully applied to extract endogenous phosphopeptides in biological sample of human saliva. As a result, 34 mono-phosphorylated peptides and 10 multi-phosphorylated peptides were detected from merely 1 mu L of pristine human saliva, confirming its bright prospects in phosphopeptidomics analysis.