Method for preparing sermorelin

Abstract

The invention discloses a method for preparing sermorelin, which comprises the following steps: firstly, coupling protective amino acids one by one from a carbon end to a nitrogen end on a solid-phaseresin carrier in the presence of a condensation reagent by a solid-phase synthesis method to synthesize 9 peptide fragment resin and 20 peptide fragment resin, condensing the solid-phase fragments according to a peptide chain sequence to obtain 29 peptide resin, according to the characteristics of R protecting groups in 29 peptide resin, selecting synchronization or sequence of removal of the R protecting groups and resin cracking, performing removal of the R protecting groups and resin cracking to finally obtain crude sermorelin peptide, and then carrying out preparative liquid phase purification and freeze-drying to obyain high-purity sermorelin. According to the method, the synthesis period is greatly shortened, racemization impurities in fragment condensation are reduced through application of special amino acids, a traditional method with low solid-phase one-by-one coupling efficiency is also avoided, a liquid-phase method with complex and tedious steps is also avoided, the costis greatly reduced, the purity is high, few byproducts are produced, product purification is facilitated, the product yield is high, and mass production operation is facilitated.

Description

technical field [0001] The invention belongs to the technical field of preparation of polypeptide drugs, and in particular relates to a method for preparing sermorelin. Background technique [0002] Sermorelin is a synthetic growth hormone releasing hormone composed of 29 amino acids, which is the amino-terminal fragment of endogenous growth hormone-releasing hormone (GHRH), and has a significant growth-regulating effect, with a molecular weight of 3357.882Da , formula C 149 h 246 N 44 o 42 S, its peptide sequence is as follows: Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu -Leu-Gln-Asp-Ile-Met-Ser-Arg-NH 2 . [0003] At present, the chemical synthesis methods of sermorelin are as follows: (1) BOC is used as the amino protecting group, and is coupled into 29 full peptide resins one by one through the solid phase, such as WO2005016953A2, US4703035; its disadvantages are obvious, and in the synthesis process HF is used to remove...

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Problems solved by technology

[0003] At present, the chemical synthesis methods of sermorelin are as follows: (1) BOC is used as the amino protecting group, and is coupled into 29 full peptide resins one by one through the solid phase, such as WO2005016953A2, US4703035; its disadvantages are obvious, and in the synthesis process HF is used to remove the resin, and the operation is very dangerous. TFA must be used for deprotection in each step. The coupling efficiency is low, the synthesis intensity is high, and the requirements for equipment and environment are high; (2) the liquid phase segment 7+7+5 is used +10, 6+4+4+4+4+7 to obtain full peptides, such as US4774319A and JPS61115098A respectively; the disadvantage is that the liquid phase reaction synthesizes medium and long peptide chains, and each step needs to be monitored and post-processed, and the experimental process is cumbersome. Conducive to workshop production

[0004] In order to overcome the defects such as difficult coupling, strong hydrophobicity, low coupling efficiency, and long cycle encountered in the solid-phase coupling process of sermorelin one by one, the present invention hopes to provide a new method for preparing sermorelin

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