A preparation method of a solid-phase synthesis medium based on a monolithic polymer material

Abstract

The invention discloses a preparation method of a solid phase synthesis medium based on integrated polymer material. The preparation method of the solid phase synthesis medium based on the integrated polymer material includes: evenly mixing styrene monomer, a cross linking agent and a pore foaming agent according to a certain proportion so as to obtain a mixture, and then injecting the mixture into a reaction mold, heating the mixture to certain temperature, and keeping the mixture in copolymerization reaction in situ at the certain temperature for a certain time so as to obtain the integrated polymer material; using a Soxhlet extraction method to process the integrated polymer material or using a method of flushing the integrated polymer material by connecting the integrated polymer material with a liquid chromatogram pump so as to remove the internal pore foaming agent of the integrated polymer material, and then obtaining integrated cellular material; using hydrophilic vinyl monomer to perform graft polymerization modification on surfaces of pore channels of the integrated cellular material; gradually deriving a large number of hydroxide radicals on a surface grafted polymer long chain, and linking the large number of the hydroxide radicals with a linker peptide reactive group so as to obtain the solid phase synthesis medium linked with a linker. The solid phase synthesis medium prepared through the preparation method of the solid phase synthesis medium based on the integrated polymer material is provided with micron through holes, has a non-swelling property high in cross linking degree, and can be applied into large scale polypeptide synthesis production.

Description

technical field [0001] The invention relates to the technical field of polymer materials, in particular to a method for preparing a solid-phase synthesis medium based on a whole polymer material. Background technique [0002] At present, since Merrifield invented this method, solid-phase synthesis has been widely used in the field of peptide and nucleic acid synthesis. Usually the key to the success of the synthesis lies in the selection of the solid-phase synthesis carrier. At present, most of the carriers used in the solid-phase synthesis are polystyrene microspheres with a low degree of crosslinking (1-2%). There is a high degree of swelling in the medium, which is conducive to the full reaction and diffusion of the reactants in it. However, the characteristics of the polystyrene matrix itself determine its hydrophobic nature, resulting in low swelling of this type of matrix in polar solvents. At the same time, when it is used to synthesize polypeptide molecules with rel...

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Problems solved by technology

[0004] 1) Use diethylene glycol dimethacrylate, tripropylene glycol diacrylate and 1,6 hexanediol diacrylate with better hydrophilicity as crosslinking agents instead of divinylbenzene (DVB) to Crosslinking styrene monomer (St) to prepare modified polystyrene microsphere medium, in DCM, NMP, DMF, THF, CHCl3, the swelling degree of Merrifield resin (PSt-DVB) is significantly increased, and the synthesis of difficult sequence acyl Carrier proteins 65-74 obtained higher yields than Merrifield resins, but in synthetic filtration operations, microsphere breakage occurred, mainly due to the decrease in molecular rigidity of these crosslinkers compared to DVB, resulting in a decrease in the mechanical strength of the resin , is not conducive to continuous operation

[0005] 2) Grafting and copolymerizing hydrophilic macromolecules with hydrophobic media, such as polystyrene grafting polyethylene glycol resin, grafting PEG macromolecules on the PSt microsphere medium, and the site of reaction with the polypeptide is located in the PEG molecular chain In this way, the PEG chains isolate the hydrophobicity of the medium body. In addition, the PEG chains grafted on these media have good solubility properties, can simulate the solution synthesis environment, and can promote the dissolution of polypeptide molecules. It is beneficial to reduce the production of incomplete peptides; however, due to the steric effect of grafting PEG molecules with a certain chain length on the PSt microsphere medium body, the substitution degree of this type of medium is low (0.2-0.3mmol / g) in large-scale The preparation of peptides is limited in application

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