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Preparation process of lixisenatide

A technology of lixisenatide and preparation process, which is applied in the field of preparation process of peptide synthesis, and can solve problems such as toxicity, increased discharge of three wastes, and environmental pollution

Active Publication Date: 2021-05-18
HANGZHOU GOTOP BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004]As a polypeptide composed of 44 amino acids, impurities are unavoidable in solid phase synthesis, and some impurities are very close to the target product in nature, so it is not easy to separate and purify , and will produce a certain degree of toxicity; while using traditional resins will increase the discharge of three wastes and pollute the environment

Method used

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  • Preparation process of lixisenatide
  • Preparation process of lixisenatide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 2

[0051] 1) Weigh 30.77g of Sieber Amide Resin (the degree of substitution is 0.65mmol / g) into the reaction column, swell with an appropriate amount of DCM for 15min, drain it and wash it with DMF three times, add an appropriate amount of decapping solution for 5min, then drain and remove the cap Wash once with an appropriate amount of DMF, then add an appropriate amount of decapping solution to react for 10 minutes, drain the decapping solution, wash 6 times with DMF, and dry it. Among them, the decapping solution is prepared by DBLK and DMF according to the volume ratio of 1:4. become.

[0052] 2) Weigh 18.74g of Fmoc-Lys(Boc)-OH and 5.40g of HOBt, completely dissolve in an appropriate amount of DMF, and then ice-bath, slowly add 6.19ml of DIC, stir while adding, return to room temperature and mix Fmoc-Lys(Boc)- The DMF fusion solution of OH and HOBt / DIC was added to the reaction column, stirred and reacted for 1 h while passing nitrogen gas, and then carried out Kaiser detect...

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Abstract

The invention discloses a preparation process of lixisenatide. Lixisenatide 1-36 fragments and lixisenatide 37-44 fragments are synthesized in sequence, then polypeptide fragments are condensed and cracked under the liquid phase condition to obtain lixisenatide crude peptide, and high-purity lixisenatide is obtained through separation and purification. According to the preparation process, the lixisenatide is condensed mainly by using a fragment method, toxic impurities are avoided, meanwhile, emission of three wastes is greatly reduced by using Sieber Amide Resin, and the preparation process is suitable for large-scale production.

Description

technical field [0001] The present invention relates to the technical field of a preparation process for polypeptide synthesis, in particular to a preparation process for lixisenatide. Background technique [0002] Diabetes is the first of the top ten chronic diseases in the world. It is a very common disease, and its pathology is caused by hyposecretion of pancreatic islets or defects in insulin action. Diabetes is divided into type I diabetes and type II diabetes, wherein type I diabetes patients are dependent on insulin, and type II diabetes patients do not need to rely on insulin. Lixisenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist and can be used to treat type II diabetes. Lixisenatide is a polypeptide composed of 44 amino acids, the molecular formula is C215H347N61O65S1, the molecular weight is 4858.49, the Cas number is 320367-13-3, and the sequence is as follows: [0003] H-His1-Gly2-Glu3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Leu10-Ser11-Lys12-Gln13-Met14-Gl...

Claims

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Application Information

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IPC IPC(8): C07K14/575C07K1/16C07K1/06C07K1/04
CPCC07K14/57563Y02P20/55
Inventor 沈永刚肖攀谢振亮付坤沈永良程益明胡桂香
Owner HANGZHOU GOTOP BIOTECH
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