Solid phase method of secretin

Abstract

The invention provides a solid phase method of secretin, which comprises the following steps: 1) selecting an appropriate solid phase carrier; 2) coupling amino acids one by one according to a solid phase synthetic method; 3) splitting for obtaining a crude peptide; 4) obtaining the secretin by purifying the crude peptide, wherein, the solid phase synthesis employs Fmoc-strategy, and false proline is used for replacing parts of serine in the peptide chain during the solid phase synthesis. The solid phase method of secretin provided by the invention has the advantages of simple operation, small impurity, easy purifying and high yield, and is beneficial to realization of industrialization.

Description

technical field [0001] The invention relates to a method for preparing polypeptide medicine in solid phase, in particular to a method for preparing secretin in solid phase, belonging to the field of medicinal chemistry. Background technique [0002] Secretin (English name Secretin) is secreted by S cells located in the upper mucosa of the duodenum and jejunum. It is a basic polypeptide with a helical structure composed of 27 amino acids. It has the functions of regulating pancreatic exocrine, inhibiting gastric acid secretion and gastric motility. and other physiological functions, its peptide sequence is H-His-Ser- [0003] 1Asp-Gly-Thr-Phe-Thr-Ser-Glu-Leu-Ser-Arg-Leu-Arg-Asp-Ser-Ala-Arg-Leu-Gl 8 16n-Arg-Leu-Leu-Gln-Gly-Leu- Val-NH 2 , also abbreviated as HSDGTFTSELSRLRDSA [0004] 24RLQRLLQGLV-NH 2 , its structural formula is as follows: [0005] [0006] The step-by-step coupling synthesis of secretin i...

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Problems solved by technology

[0007] Helv.Chim.Acta1976,1112, Int.J.Peptide Protein Res,1977,63), the solid phase adopts Boc-strategy (Int.J.Peptide Protein Res,1977,63) to synthesize secretin, in the solid phase Boc-strategy, Repeatedly using acid to deprotect, this treatment has brought the following problems: For example, at the junction of the peptide and the resin, when 50% TFA is used to de-Boc each time, about 1.4% of the peptide is released from the resin, and the synthetic The larger the peptide, the more serious the loss; in addition, acid catalysis will cause some side reactions in the side chain, and the Boc synthesis method is especially not suitable for the synthesis of acid-labile peptides containing tryptophan.

[0010] Although the above-mentioned prior art can be used for the synthesis of secretin, the yield is relatively low, wherein, the synthetic total yield of the liquid-phase step-by-step coupling of secretin is less than 10%; the solid-phase Boc-strategy synthetic total yield is less than 20%; The synthesis strategy of Arg protected by perchloric acid has a total yield of less than 30%

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