Preparation method of Plecanatide

A prika, crude peptide technology, applied in the preparation methods of peptides, chemical instruments and methods, peptides, etc., can solve the problems of difficult separation and purification, methods to be improved, complex components, etc., and achieve considerable economic and practical value and cost. Low, high yield effect

Active Publication Date: 2015-05-20
NANJING UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since the ring formation of this method is carried out twice in the solution, the components in the solution are complex, and the separation and purification are difficult, so the method needs to be improved.

Method used

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  • Preparation method of Plecanatide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Weigh 10 g (5.1 mmol) of Fmoc-Leu-king resin with a degree of substitution of 0.51 mmol / g, add it to the solid phase reactor, wash with DMF three times, and swell for 3 hours. The piperidine:DMF solution with a volume ratio of 1:4 was added to the reactor for reaction, and after the reaction, it was washed twice with DCM, and washed with DMF four times. Weigh 6.34g of Fmoc-Cys(Acm)-OH, 2.07g of HOBt, and 2.37mL of DIC to dissolve in DMF solution, mix well and add to the reactor, and react at room temperature for 2h. The ninhydrin color reaction controls the end point. The resin is transparent and colorless to indicate the end of the reaction. If the color develops, the reaction continues until colorless. After the reaction was completed, DCM was washed twice, and DMF was washed four times.

[0045] Repeat the above steps, follow the sequence of deprotection, coupling Fmoc-Gly-OH, Fmoc-Thr(tBu)-OH, Fmoc-Cys-(Mmt)-OH, Fmoc-Ala-OH, Fmoc-Val-OH , Fmoc-Asn(Trt)-OH, Fmoc-Val-O...

Embodiment 2

[0051] Weigh 10 g (2 mmol) of Fmoc-Leu-king resin with a degree of substitution of 0.2 mmol / g and add it to the solid phase reactor. After DMF was washed 3 times, it swelled for 3 hours. The piperidine:DMF solution with a volume ratio of 1:4 was added to the reactor for reaction, and after the reaction, it was washed twice with DCM, and washed with DMF four times. Weigh 1.24g of Fmoc-Cys(Acm)-OH, 0.406g of HOBt, and 0.465mL of DIC to dissolve in DMF solution, mix well and add to the reactor, and react at room temperature for 2h. The ninhydrin color reaction controls the end point. The resin is transparent and colorless to indicate the end of the reaction. If the color develops, the reaction continues until colorless. After the reaction was completed, DCM was washed twice, and DMF was washed four times.

[0052] Repeat the above steps, follow the sequence of deprotection, coupling Fmoc-Gly-OH, Fmoc-Thr(tBu)-OH, Fmoc-Cys-(Mmt)-OH, Fmoc-Ala-OH, Fmoc-Val-OH , Fmoc-Asn(Trt)-OH, Fmo...

Embodiment 3

[0058] Weigh 10 g (6 mmol) of Fmoc-Leu-king resin with a degree of substitution of 0.6 mmol / g, add it to the solid phase reactor, wash with DMF three times, and swell for 3 hours. The piperidine:DMF solution with a volume ratio of 1:4 was added to the reactor for reaction, and after the reaction, it was washed twice with DCM, and washed with DMF four times. Weigh 7.46g of Fmoc-Cys(Acm)-OH, 2.44g of HOBt, and 2.79mL of DIC, and dissolve them in DMF solution, mix well and add to the reactor, and react at room temperature for 2h. The ninhydrin color reaction controls the end point. The resin is transparent and colorless to indicate the end of the reaction. If the color is developed, the reaction continues until colorless. After the reaction was completed, DCM was washed twice, and DMF was washed four times.

[0059] Repeat the above steps, follow the sequence of deprotection, coupling Fmoc-Gly-OH, Fmoc-Thr(tBu)-OH, Fmoc-Cys-(Mmt)-OH, Fmoc-Ala-OH, Fmoc-Val-OH , Fmoc-Asn(Trt)-OH, Fm...

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Abstract

The invention discloses a preparation method of Plecanatide. The preparation method comprises the following steps: 1) preparing side chain group protected peptide resin from Fmoc-Leu-resin by coupling one by one from the carbon end to nitrogen end by a Fmoc solid-phase synthesis method according to the polypeptide sequence order of Plecanatide; 2) de-protecting the peptide resin respectively according to an order of Cys4-Cys12 and Cys7-Cys15 to obtain all-protected Plecanatide resin; 3) cracking the side chain group protected peptide resin by use of a cracking reagent; and 4) desalting and performing purification and freeze drying to obtain Plecanatide. The Plecanatide preparation method disclosed by the invention has practical industrial application prospects and considerable economic practical values.

Description

Technical field [0001] The invention belongs to the technical field of pharmacy, and in particular relates to a method for preparing prikanatide through a directional ring formation reaction on a resin. Background technique [0002] The C-type guanylate cyclase (GC-C) receptor is mainly expressed on the lumen side of small intestinal epithelial cells. GC-C is a multi-center enzyme, including extracellular ligand binding domain, single channel transmembrane domain, active center similar to tyrosine kinase protein, and ligand-mediated activation of the C-terminal GC-C catalyst to generate cGMP area. Enterotoxin (ST) causes secretory diarrhea in the affected population by overactivating the signal channel of the intestinal receptor GC-C (the only ST target in the body that has been confirmed). Correspondingly, knocking out the mouse GC-C encoding gene resulted in the suppression of ST-induced intestinal secretion and diarrhea. Infectious diarrhea caused by ST-producing bacteria i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/08C07K1/06C07K1/04
CPCY02P20/55
Inventor 朱颐申周云隆韦萍欧阳平凯
Owner NANJING UNIV OF TECH
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