Cracking liquid for peptide resin, and application thereof in synthesizing somatostatin by solid phase cracking

A technology of somatostatin and lysate, applied in the production of peptides and bulk chemicals, etc., to achieve the effects of reducing production costs, obvious economic benefits, and improving conversion rates

Active Publication Date: 2014-08-06
HYBIO PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in the above-mentioned solid-phase polypeptide synthesis methods, the classic lysate ratio is used to prepare the lysate, so as to complete the synthesis of somatostatin, such as CN1508152A, CN1552728A and CN1923851A, etc., there is little about improving the lysate, and then effectively improve Reporting of Oxidation Reaction Yields

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Embodiment 1: the synthesis of peptide resin

[0025] Take by weighing 2-CTC resin 15.38g (10.0mmol) that substitution degree is 0.65mmol / g, join in the solid-phase reaction column, wash 2 times with DMF, after 30 minutes with DMF swelling resin, get 11.714g Fmoc-Cys ( Trt)-OH (20.0mmol) was dissolved in DMF, activated by adding 6.6mL DIEA (40mmol) in an ice-water bath, added to the above-mentioned reaction column equipped with resin, reacted for 2 hours, added 20mL of anhydrous methanol to seal for 1 hour, and used DMF Wash 6 times. Fmoc protection was deprotected with DBLK for 15 min + 15 min, followed by 6 washes with DMF.

[0026] Dissolve 7.668g Fmoc-Ser(tBu)-OH (20mmol), 2.702g HOBt (20mmol), 3.08ml DIC (20mmol) in 60ml of DCM and DMF mixed solution with a volume ratio of 1:1, and add it to the solid phase reaction column , and react at room temperature for 2 hours (the end point of the reaction is determined by the ninhydrin method. If the resin is colorless an...

Embodiment 2

[0027] Example 2: Cleavage of Peptide Resin

[0028] The peptide resin 41.70g that embodiment 1 obtains is added in the 1000ml flask, configures 400ml lysate TFA:EDT:H 2 O=85:10:5, V / V, add the lysate into the flask, react at room temperature for 2.5 hours, after the reaction is over, filter the resin and collect the filtrate. The resin was washed with a small amount of TFA, the filtrate was combined, and the filtrate was added to 4000ml of anhydrous ether to precipitate, centrifuged, washed with anhydrous ether, and vacuum-dried to obtain 16.21g of somatostatin linear crude peptide, with a linear crude peptide yield of 98.8%. MS=1639.9.

Embodiment 3

[0029] Example 3: Cleavage of Peptide Resin

[0030] The peptide resin 41.70g that embodiment 1 obtains is added in the 1000ml flask, configures 400ml lysate TFA:EDT:H 2 O=85:5:10, V / V, put the lysate into the flask, react at room temperature for 2.5 hours, after the reaction is over, filter the resin and collect the filtrate. The resin was washed with a small amount of TFA, the filtrate was combined, and the filtrate was added to 4000ml of anhydrous ether to precipitate, centrifuged, washed with anhydrous ether, and vacuum-dried to obtain 16.11g of somatostatin linear crude peptide, and the linear crude peptide yield was 98.2%. MS=1639.9.

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PUM

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Abstract

The invention belongs to the technical field of medicine synthesis, and discloses a cracking liquid for a peptide resin. The cracking liquid comprises, by volume, 85%-90% of trifluoroacetic acid (TFA), 0%-10% of 1,2-ethanedithiol (EDT), 0%-10% of water and 0-10% of methyl-phenoxide (PhOMe), wherein at least two components of EDT, water and PhOMe are not 0 at the same time. Besides, the invention discloses a method for preparing somatostatin and an application of the cracking liquid in synthesizing the somatostatin, wherein the cracking liquid is used for a cracking reaction. Analytical comparison tests show that by adopting the improved cracking liquid to crack the solid-phase synthesis resin, crude peptide purity and conversion rate of peptide oxide are effectively increased; a yield of an oxidation reaction is increased by about 10%. Therefore, the cracking liquid has obvious economic benefits and can effectively reduce production cost.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a lysate for peptide resin and its application in solid-phase cleavage synthesis of somatostatin. Background technique [0002] Somatostatin, that is, growth hormone release inhibitory factor, the English name is Somatostatin, and the molecular formula is C 76 h 104 N 18 o 19 S 2 , the molecular weight is 1637.890. It is an endogenous regulatory hormone that exists in the human body, and has a wide range of inhibitory effects on various physiological functions. The simplified formula of amino acid structure is: [0003] Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys (disulfide bond). [0004] The chemical structure of somatostatin is fourteen peptides with a pair of disulfide bonds in the molecule. It mainly exists in the central nervous system and peripheral organs (such as: stomach, intestine, membrane, skin, etc.) in the human body. The maximum concentrat...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/08
CPCY02P20/55
Inventor 张文治刘建马亚平袁建成
Owner HYBIO PHARMA
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