Synthesizing method of sermaglutide

A technology of semaglutide and synthesis method, which is applied in the field of peptide synthesis, can solve problems such as the synthesis of difficult sequences of semaglutide, and achieve the effects of solving coupling difficulties, reducing costs, and reducing material input

Active Publication Date: 2018-10-19
SINOPEP ALLSINO BIOPHARMACEUTICAL CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0011] In order to solve the deficiencies in the prior art, the object of the present invention is to provide a synthetic method of semaglutide, which introduces Depsipeptide Units to solve the problem of difficult sequence synthesis of semaglutide, and then obtains the target product through the reaction of ester bond to amide bond ; The synthetic method of the present invention has improved the purity and the yield of crude peptide, is beneficial to downstream purification, is suitable for industrialized production

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  • Synthesizing method of sermaglutide
  • Synthesizing method of sermaglutide
  • Synthesizing method of sermaglutide

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Embodiment Construction

[0059] The present invention will be specifically introduced below in conjunction with the accompanying drawings and specific embodiments.

[0060] There are two options for preparing semaglutide:

[0061] Such as figure 1 Option 1 shown;

[0062] A synthetic method for semaglutide, comprising the steps of:

[0063] Step 1, prepare Fmoc-Gly-Wang resin;

[0064] Step 2, preparing fully protected peptide resin;

[0065] Step a, preparing protected amino acid fragments,

[0066] The chemical structural formula of the protected amino acid fragment is:

[0067] Where R includes: H, CH 3 (Ser,Thr); Thr in peptide sequence 5 、Thr 7 、Ser 8 、Ser 11 、Ser 12 .

[0068] Written as a chemical formula: Boc-Thr 5 (Fmoc-Gly 4 )-OH, Boc-Thr 7 (Fmoc-Phe 6 )-OH, Boc-Ser8(Fmoc-Thr 7 (tBu))-OH, Boc-Ser 11 (Fmoc-Val 10 )-OH, Boc-Ser 12 (Fmoc-Ser 11 (tBu))-OH.

[0069] Step b, Fmoc-Gly-Wang resin is added in the solid phase reactor;

[0070] Step c, adding the single protect...

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Abstract

The invention discloses a synthesizing method of sermaglutide. The synthesizing method comprises the following steps of step 1, preparing Fmoc-Gly-Wang resin; step 2, using the Fmoc-Gly-Wang resin, protective amino acids, and octadecandioic acid (OtBu)-gamma-Glu-OtBu-PEG-PEG-OH as the raw materials to prepare full-protective peptide resin which contains Depsipeptide Units; step 3, performing TFA (trifluoroacetic acid) cracking on the peptide resin, so as to obtain crude peptide; step 4, dissolving the crude peptide obtained in step 3, adjusting the pH (potential of hydrogen) value, and converting ester bonds into amide bonds to react, so as to obtain a crude product of the sermaglutide. The synthesizing method has the advantages that by introducing the Depsipeptide Units, the problem of difficulty in sequential synthesizing of the sermaglutide is solved, and the target product is obtained by the reaction of converting the ester bonds into the amide bonds; the purity and yield of the crude peptide are improved, and the synthesizing method is suitable for downstream purifying, and is suitable for industrialized production.

Description

technical field [0001] The invention relates to the field of polypeptide synthesis, in particular to a method for synthesizing semaglutide. Background technique [0002] Chinese name: semaglutide [0003] English name: Sermaglutide [0004] The peptide sequence is: [0005] H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys(Octadecanedioic-γ-Glu-PEG2- PEG2)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH; [0006] Semaglutide is a new long-acting GLP-1 analog developed by Novo Nordisk, Denmark. From the amino acid sequence, the 2nd position of the peptide sequence is the unnatural amino acid amino isobutyric acid, and the Lys side chain amino group at the 20th position of the peptide sequence is Modified with PEG, γ-Glu and octadecanedioic acid. Compared with semaglutide, the modified semaglutide has enhanced hydrophilicity, inhibits the hydrolysis of DPP-4 enzyme, prolongs the biological half-life, lowers blood sugar for a long time, promo...

Claims

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Application Information

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IPC IPC(8): C07K14/605C07K1/06C07K1/04
CPCC07K14/605
Inventor 赵呈青谷海涛施国强王蔡典玄其存
Owner SINOPEP ALLSINO BIOPHARMACEUTICAL CO LTD
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