Method for solid phase polypeptide synthesis of hexarelin

A technology for solid-phase polypeptide synthesis and hexarelin, which is applied in the field of preparation of solid-phase polypeptide synthesis hexarelin, can solve the problems of long synthesis cycle and use of highly toxic substances, and achieve low production cost, reduction of three wastes, and process stable effect

Active Publication Date: 2011-07-20
GL BIOCHEM SHANGHAI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The purpose of the present invention is to provide a method for synthesizing hexarelin with a phase polypeptide, which mainly solves the technical problems of long synthesis period and the use of highly toxic substances in the existing synthesis method

Method used

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  • Method for solid phase polypeptide synthesis of hexarelin
  • Method for solid phase polypeptide synthesis of hexarelin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] (1) Preparation of Fmoc-Lys(Boc)-Linker AM Resin

[0051] Weigh 1g of Fmoc-Linker-AM Resin (Loadding: 0.6mmol / g) into a 30ml peptide bottle, add about 15ml of DCM to the resin, soak for 10 minutes (at room temperature) and dry it with a vacuum pump, add 10ml of decapping reagent and put it in a constant temperature oscillator React for 5 minutes, dry with a vacuum pump, re-add 10ml of capping agent and react for 15 minutes (30°C-40°C), dry with a vacuum pump, wash with industrial-grade DMF for 3 times, wash with anhydrous methanol for 3 times, and re-evaporate Wash with DCM for 3 times, add Fmoc-Lys(BOC)-OH0.702g, HOBt0.337g, analytical grade DMF8ml, DIC0.2ml, Collidine0.3ml to react for 40 minutes (30℃~50℃), use vacuum pump to dry, Industrial-grade DMF was washed 3 times, anhydrous methanol was washed 3 times, redestilled DCM was washed 3 times, and dried to obtain Fmoc-Lys(Boc)-LinkerAM Resin;

[0052] (2) Preparation of Fmoc-D-Phe-Lys(Boc)-Linker AM Resin

[0053] ...

Embodiment 2

[0070] Adopt the same method and processing condition as embodiment 1, wherein:

[0071] Use Fmoc-Linker-MBHA Resin as the starting material, add decapping reagent and react at 30-50°C for 5 minutes, drain, add decapping reagent again and react for 15 minutes, wash, add Fmoc-amino acid, analytical grade DMF, Collidine, DIC / HOBt or DIC / HOAt or BOP / HOBt or BOP / HOAt or HBTU / HOBt or HBTU / HOAt or HATU / HOBt or HATU / HOAt or HCTU / HOBt or HUTC / HOAt or TBTU / HOBt, reaction 40 minutes, with embodiment 1 Operate until the hexapeptide is finished. After cutting and other reactions, 0.540 g of white powder product was obtained.

Embodiment 3

[0073]Weigh 50g of Fmoc-Linker-AM Resin or Fmoc-Linker-MBHA Resin (Loadding: 0.7mmol / g) and pour it into a 600ml peptide bottle, add the decapping reagent at 30-50°C for 5 minutes, drain it, and add the decapping reagent again for 15 minutes min, wash, add Fmoc-amino acid, analytical grade DMF, Collidine, DIC / HOBt or DIC / HOAt or BOP / HOBt or BOP / HOAt or HBTU / HOBt or HBTU / HOAt or HATU / HOBt or HATU / HOAt or HCTU / HOBt or TBTU / HOBt, react for 40 minutes, operate with embodiment 1, until the hexapeptide is connected. After cutting and other reactions, 33g of white powder product was obtained. The purity of the crude product reacted with HBTU / HOBt will be better.

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Abstract

The invention relates to a preparation method of hexarelin, and mainly solves the technical problems with long synthetic period and applications of hypertoxic substances in the prior synthetic method. The method for synthesizing the hexarelin by adopting the solid phase polypeptide synthetic method comprises the steps as follows: Fmoc-Linker-AM-Resin or Fmoc-Linker-MBHA-Resin is adopted as the initial raw material; amino acids with Fmoc protective groups are sequentially connected according to the solid phase polypeptide synthetic method to obtain a protected six peptide resin, while the Fmocprotective groups are sequentially removed and a peptide synthetic reaction is carried out in the presence of one of DIC / HOBt, DIC / HOAt, BOP / HOBt, BOP / HOAt, HBTU / HOBt, HBTU / HOAt, HATU / HOBt, HATU / HOAtor HCTU / HOBt as a condensing agent; side chain protective groups removal and peptide cutting are carried out synchronously to obtain a coarse product; the coarse product is subjected to separation and purification to obtain the hexarelin which is further subjected to lyophilization to obtain hexarelin acetate or trifluoroacetate product. The method is applicable to the large-scale hexarelin production.

Description

Technical field: [0001] The invention relates to a preparation method of hexarelin (including acetate and trifluoroacetate), in particular to a preparation method of solid-phase polypeptide synthesis of hexarelin. Background technique: [0002] Hexarelin, Chinese name: Haisha Ruilin, English name: Hexarelin [0003] Structural formula: His-D-2-Me-Trp-Ala-Trp-D-Phe-Lys-NH 2 [0004] Molecular formula and molecular weight: C47H58N12O6; 887.0 [0005] In recent years, studies have found that the loss of cardiomyocytes caused by apoptosis is one of the important mechanisms of heart failure. Angiotensin II (Angiotension II) is an important neuroendocrine factor in the occurrence of heart failure, which can induce cardiomyocyte apoptosis. A large number of data show that hexarelin has a significant protective effect on the cardiovascular system. Studies have shown that Hexarelin can significantly inhibit AngII-induced cardiomyocyte apoptosis. Cardiomyocyte hypertrophy is one ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K1/04C07K1/06
CPCY02P20/55
Inventor 徐红岩金健林姜培娟
Owner GL BIOCHEM SHANGHAI
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