Magnetic metal-organic framework nanosphere with multiple affinity sites as well as preparation method and application thereof

Abstract

The invention discloses a magnetic metal-organic framework nanosphere with multiple affinity sites as well as a preparation method and application thereof. The magnetic metal-organic framework nanosphere consists of a Fe3O4 magnetic sphere, a high-molecular polymer intermediate layer coating the surface of the magnetic sphere, a metal-organic framework growing on the high-molecular polymer intermediate layer and arginine grafted on the metal-organic framework. The magnetic metal-organic framework nanosphere disclosed by the invention takes the Fe3O4 magnetic sphere as a kernel and has good magnetic response performance; the metal-organic framework is introduced onto the surface of the magnetic sphere, and the organic ligand surface is modified through the arginine; as metal ions forming the metal-organic framework, a guanidyl on the arginine and the like can be taken as the multiple affinity sites for enriching phosphorylated polypeptides, the enrichment of the phosphorylated polypeptides for single-phosphorylation sites and multi-phosphorylation sites is achieved; the magnetic metal-organic framework nanosphere has high enrichment efficiency and has very important significance in studying the phosphorylation process of physiological behavioral proteins.

Description

technical field [0001] The invention belongs to the technical field of biomaterials, and relates to a magnetic metal-organic framework nanosphere and a preparation method and application thereof. Background technique [0002] Magnetic metal-organic framework nanospheres are composed of magnetic nanospheres and metal-organic frameworks (Metal-Organic Frameworks, MOFs) wrapped on the surface of magnetic nanospheres, which not only have good magnetic response performance, but also have the high porosity of MOFs , excellent mechanical properties, abundant aromatic ligands and easy adjustment of surface properties and other unique properties, therefore, magnetic metal-organic framework nanospheres have attracted much attention in recent years and have been widely used in the field of biomedicine, especially in the separation of proteins or peptides, drug transmission, magnetic resonance imaging, etc. [0003] Magnetic metal-organic framework nanospheres are usually prepared by l...

AI Technical Summary

Problems solved by technology

[0003] Magnetic metal-organic framework nanospheres are usually prepared by layer-by-layer self-assembly technology: (1) Document FacilePreparation of Core-Shell Magnetic Metal-Organic Framework Nanoparticles for the Selective Capture of Phosphopeptides (ACS Appl.Mater.Interfaces 2015,7, 16338-16347, Weibing Zhang etc.) disclose a kind of preparation method of magnetic metal-organic framework nanosphere, with Fe 3+ As the metal ion and trimethylbenzene as the organic ligand, the magnetic nanospheres were first coated with methyl methacrylate (MMA), and then the magnetic nanospheres were added to the Fe 3+ Stir in the solution for 15 minutes, then take it out and wash it, and then stir in the trimethylbenzene solution for 30 minutes to complete a self-assembly. Repeat this 31 times to obtain magnetic metal-organic framework nanospheres. Although this method can regulate the metal-organic framework The thickness of the layer, but its operation is very cumbersome and time-consuming, which is not conducive to mass production; (2) Literature Fabrication of a magnetic nanoparticle embedded NH 2 -MIL-88BMOF hybrid for highly efficient covalent immobilization of lipase (RSC Adv., 2016, 6, 66385–66393, Sumanta Kumar Sahu, etc.) discloses a preparation method of magnetic metal-organic framework nanospheres, directly adding magnetic nanospheres , a solution containing metal ions and an organic ligand are added to a reaction kettle filled with dimethylformamide (N,N-Dimethylformamide, DMF) solvent, and the magnetic metal- Organic framework nanospheres, although the preparation method is relatively simple and the operation steps are few, the magnetic metal-organic framework nanospheres obtained by it have poor morphology, and it is difficult to control the morphology by adjusting the experimental parameters, and the high temperature and high pressure conditions are relatively low. Harsh and difficult to regulate; (3) Literature The design and synthesis of a hydraulic core–shell–shell structured magnetic metal-organic framework as a novelimmobilized metal ion affinity platform for phosphoproteome research (Chem.Commun.,2014,50,6228-6231 , Chunhui Deng, etc.) disclosed a method for preparing magnetic metal-organic framework nanospheres, first coating a layer of Zr on the surface of ferroferric oxide 4+ Polydopamine (PDA) with chelating effect on metal ions, and then grow a layer of metal-organic framework in situ on the surface of superparamagnetic ferric iron tetroxide wrapped with PDA through a one-pot method, and finally obtain a regular shape Magnetic metal-organic framework nanospheres, this method utilizes a polymer layer to chelate metal ions, thereby facilitating the in situ growth of metal-organic frameworks, which is crucial for the synthesis of magnetic metal-organic framework nanospheres, however due to Due to the high viscosity of PDA itself, the agglomeration phenomenon of the magnetic balls wrapped with PDA on the surface is relatively obvious, and the dispersion performance is poor, which is not conducive to the synthesis of the metal-organic framework on the surface of the magnetic balls in the next step.

On the other hand, the chelating effect of PDA on divalent or trivalent metal ions is not as strong as that on tetravalent metal ions, which limits its application in the preparation of magnetic metal-organic framework nanospheres to a certain extent.

[0004] In addition, from the perspective of the application of magnetic metal-organic framework nanospheres to the enrichment of phosphorylated polypeptides (polypeptides with phosphorylated groups), almost all affinity sites for enriching phosphorylated polypeptides only use magnetic metal-organic frameworks. Metal ions in the organic framework structure (see literature Facile Preparation of Core-Shell Magnetic Metal-Organic Framework Nanoparticles for the Selective Capture of Phosphopeptides, ACS Appl. Mater. Interfaces 2015, 7, 16338-16347, Weibing Zhang et al. and The design and synthesis of a hydrophilic core–shell–shell structured magnetic metal-organic framework as a novel immobilized metal ion affinity platform for phosphoproteome research, Chem.Commun., 2014, 50, 6228-6231, Chunhui Deng, etc.), while ignoring the magnetic metal-organic A large number of organic ligands in the framework structure make the enrichment efficiency of magnetic metal-organic framework nanospheres for phosphorylated polypeptides low, which in turn limits the application of magnetic metal-organic framework nanospheres in the separation and enrichment of biomedical protein peptides

Images