Synthesis process of thymalfasin

Abstract

The invention provides a synthesis process of thymalfasin and belongs to the field of solid phase polypeptide synthesis. The synthesis process of the thymalfasin is characterized in that firstly, AM resin is transformed, two to six side chain protection hydrophilic amino acid residues are coupled to the AM resin, and Lys, Arg, Glu, and Asp amino acid serve as the hydrophilic amino acid; and then, Rink amide Linker is coupled to the resin, and Fmoc-AAn...AA2-AA1-AM resin is prepared. The linear distance between synthetic polypeptide and the resin is prolonged, and hydrophilia of the resin is increased; the transformed resin is used for the synthesis of the thymalfasin, thymalfasin solid phase synthesis adopts the linear continuous synthesis from C terminal to N terminal; the best synthesis efficiency is obtained by controlling the amino acid excess multiple and the coupling time; after peptide chain synthesis is finished, Fmoc protection is removed; acetic anhydride acetylizes polypeptide N-terminal; decomposition is conducted through a cracking reagent; and the thymalfasin is obtained after diethyl ether precipitating. According to the synthesis process of the thymalfasin, the prepared resin performs efficiently when the thymalfasin synthesis is carried out, and the beta sheet of the thymalfasin is eliminated well in the process of the solid phase synthesis.

Description

technical field [0001] The invention relates to solid-phase polypeptide synthesis, in particular to a novel solid-phase synthesis process of the thymus method. Background technique [0002] Thymalfasin is a polypeptide of 28 amino acid residues isolated from thymus. The N-terminus of the polypeptide is acetylated, and the C-terminus is a free carboxyl group. The molecular weight is 3108Da. Thymofasin promotes the differentiation of bone marrow stem cells and induces the differentiation and maturation of T lymphocytes. Studies have shown that thymofasin is the most biologically active component of thymosin and is an ideal immune regulator. At present, Thymofasin has been used in the treatment of chronic viral hepatitis, liver cancer and immunocompromised diseases. [0003] At present, the new synthetic method of the thymus method mainly adopts Fmoc solid-phase synthesis, and there are many methods of synthesis using hydroxyl resins, such as Chinese patent CN102199205A. There...

AI Technical Summary

Problems solved by technology

[0003] At present, the new synthetic method of the thymus method mainly adopts Fmoc solid-phase synthesis, and there are many methods for the synthesis of hydroxyl resins, such as Chinese patent CN102199205A. There is a certain proportion of DKP in this method, which leads to a decline in yield. Difficult polypeptides form β-sheets during the synthesis process, resulting in difficult synthesis, low purity and yield; Chinese patent CN201410105039 can better inhibit the occurrence of DKP by adding 0-8 amino acids to Wang resin and then connecting HMPA Linker , to increase the yield

Another method uses amido resin, such as Chinese patent CN101104638A, by coupling Fmoc-Asp-OtBu, the synthesis of the rest of the amino acid is consistent with hydroxyl resin, this method can effectively eliminate the occurrence of DKP, so that the yield and purity are improved. However, due to the existence of difficult sequences, it leads to high synthesis costs and difficult separation of impurities.

Images