Metal-organic framework/3,3',5,5'-tetramethylbenzidine based multidimensional spectral array platform for sensitive discrimination of protein phosphorylation

A multifunctional metal-organic framework (MOF) hybrid Zr-FeTCPP-MOF is fabricated with 2-aminoterephthalic acid (NH₂-BDC) and Fe (III) meso-Tetra (4-carboxyphenyl) porphine chloride (FeTCPPCl) participating in the coordination to Zr₆ clusters via one-pot hydrothermal method. The adsorption of phosphoproteins on the surface of Zr-FeTCPP-MOF hybrid cause the chances on the absorbance (Abs), fluorescence (FL) and resonance light scattering (RLS) signals of Zr-FeTCPP-MOF/3,3',5,5'-Tetramethylbenzidine (TMB) system, and an array sensing platform is successfully built for sensitive identification of protein phosphorylation based on the three-dimensional spectral changes of MOF/TMB sensing system induced by the variations on the structure, size, and phosphorylation site of phosphoproteins. This array sensing system is robust in recognizing different phosphoprotein species, and shows high sensitivity in discriminating similar phosphoproteins of different phosphorylation distribution, i.e., caseins (α-, β- and κ-cas). The detection limit of this array sensing platform to individual phosphoprotein is low down to 5 nM. The practical application of this MOF/TMB-base sensing system is substantially demonstrated by identifying tau peptides with different phosphorylation distribution, and distinguishing cancer cells of abnormal phosphorylations from normal cells. This work proves the reliability, sensitivity, and practicality of the MOF/TMB-base sensing system platform for the diagnosis of phosphorylation-related diseases in clinical trials.