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Novel method for synthesizing polypeptide containing aspartic acid-arginine and derivate units

A technology of aspartic acid and arginine, applied in the preparation method of peptides, chemical instruments and methods, peptides, etc., can solve problems such as failure

Active Publication Date: 2012-01-04
北京中科亚光生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] This phenomenon is caused by the basicity of the side chain guanidine group of arginine, which works together with the basic PIPE molecule to greatly promote the occurrence of asparagine on the adjacent aspartic acid during the synthesis process. Possibility of amine side reactions leading to total failure of the entire synthesis

Method used

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  • Novel method for synthesizing polypeptide containing aspartic acid-arginine and derivate units
  • Novel method for synthesizing polypeptide containing aspartic acid-arginine and derivate units
  • Novel method for synthesizing polypeptide containing aspartic acid-arginine and derivate units

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Experimental program
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Effect test

Embodiment 1

[0026] The sequence of polypeptide 3 is Biotin-Gly-Asp-[Arg(Me) 2 ]-Gly-Gly-Phe-Gly-Pro-Gly-Lys-Met-Asp-Ser-Arg-Gly-Glu-His-Arg-Gln-Asp-Arg-Arg-Glu-Arg-Pro-Tyr-OH. Since Asp-[Arg(Me) 2 ] unit, the Asp residue is extremely prone to the side reaction of forming asparagine, which leads to the inability to prepare the target polypeptide molecule by traditional methods. Adopt solid-phase synthesis sequence Biotin-Gly-Asp on CTC resin, cut 1 hour in 1 volume % trifluoroacetic acid / dichloroethane, filtrate is added to 10 times amount of petroleum ether / anhydrous ether (1: 1, v / In v), the polypeptide is precipitated, centrifuged and dried to obtain the crude Biotin-Gly-Asp(OtBu)-OH. Combine this fragment with H-[Arg(Me) 2 ]-Gly-Gly-Phe-Gly-Pro-Gly-Lys(Boc)-Met-Asp(OtBu)-Ser(tBu)-Arg(Pbf)-Gly-Glu(OtBu)-His(Trt)-Arg( Pbf)-Gln(Trt)-Asp(OtBu)-Arg(Pbf)-Arg(Pbf)-Glu(OtBu)-Arg(Pbf)-Pro-Tyr(tBu)-King resin for fragment condensation to get the whole target The sequence of the polypeptide...

Embodiment 2

[0028] The sequence of polypeptide 4 is Biotin-Gly-Asp-Arg-Gly-Gly-Phe-Gly-Pro-Gly-Lys-Met-Asp-Ser-Arg-Gly-Glu-His-Arg-Gln-Asp-[Arg( Me) 2 ]-ArgGlu-Arg-Pro-Tyr-OH. Since Asp-[Arg(Me) 2 ] unit, the Asp residue is extremely prone to the side reaction of forming asparagine, and the target polypeptide molecule cannot be prepared by traditional methods. Solid-phase synthesis of the sequence Biotin-Gly-Asp-Arg-Gly-Gly-Phe-Gly-Pro-Gly-Lys-Met-Asp-Ser-Arg-Gly-Glu-His-Arg-Gln-Asp on CTC resin -OH, cleaved in 1 volume% trifluoroacetic acid / dichloroethane for 1 hour, the filtrate was added to 10 times the amount of petroleum ether / anhydrous ether (1:1, v / v) to precipitate the polypeptide, and dried after centrifugation. That is to obtain Biotin-Gly-Asp(OtBu)-Arg(Pbf)-Gly-Gly-Phe-Gly-Pro-Gly-Lys(Boc)-Met-Asp(OtBu)-Ser(tBu)-Arg(Pbf)- Crude Gly-Glu(OtBu)-His(Trt)-Arg(Pbf)-Gln(Trt)-Asp(OtBu)-OH. Combine this fragment with H-[Arg(Me) 2 ]-Arg(Pbf)-Glu(OtBu)-Arg(Pbf)-Pro-Tyr(tBu)-Wang res...

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Abstract

The invention relates to a novel strategy for preparing aspartic acid-arginine derivate [Asp-Arg(X)] units, and a product obtained thereby. The novel strategy is especially applicable to a polypeptide sequence which can promote the subsidiary reaction of asparaginimide in the synthesis process of arginine or arginine derivates. The method comprises a strategy for optimizing polypeptide synthesis conditions based on a fragment condensation method. In such strategy, the polypeptide sequence is divided into two fragments at Asp-Arg(X), and the two fragments are respectively synthesized, wherein one fragment containing the Asp residue is synthesized on 2-chlorotrityl chloride resin (CTC resin) extremely sensitive to acid, and the fully-protected fragment (both the N terminals and side chains are protected) obtained by preparation is coupled onto an amino group of the Arg(X) of the other fragment, thus finishing the synthesis of the whole sequence. The coarse peptide obtained by cutting ispurified by the conventional high performance liquid chromatography, thus ultimately obtaining the pure target polypeptide product. The method effectively suppresses the promotion effect of alkaline guanidyl side chains of Arg(X) on the subsidiary reaction of asparaginimide, and greatly improves the synthesis success rate of the polypeptide and the purity of the final product.

Description

technical field [0001] The present invention relates to a new method for preparing polypeptides containing aspartic acid-arginine and derivatives [Asp-Arg(X)] units in the sequence in solid-phase synthesis of polypeptides, especially suitable for arginine or arginine The presence of amino acid derivatives leads to polypeptide sequences susceptible to asparagine side reactions during synthesis, and the products obtained by this method. Background technique [0002] With the completion of the Human Genome Project, the annotation and confirmation of human genes has become one of the most important tasks facing life sciences. Proteins are the functional executives of life activities, and most of the genes and their functions in the human genome have yet to be revealed and elucidated at the protein level. Therefore, proteome research has become one of the focuses of life sciences in the 21st century. It will reveal the essence of life activities in a panoramic manner, especially...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K1/06C07K1/04C07K1/20
CPCY02P20/55
Inventor 张新军张文涛
Owner 北京中科亚光生物科技有限公司
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