Preparation method for uniform cyclic peptide Cyclo-(Cys)6

A technology of cyclic peptide and resin, which is applied in the field of cyclic peptide compound cyclic peptide Cyclo-6 and its synthesis and preparation, to achieve the effect of simple operation, good reactivity and reasonable process

Active Publication Date: 2017-12-15
INST OF NUCLEAR PHYSICS & CHEM CHINA ACADEMY OF
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] In recent years, 2-(7-azobenzotriazole)-tetramethyluronium hexafluorophosphate (HATU), benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate Fluorophosphate (HBTU), 1-hydroxybenzotriazole (HOBt), O-benzotriazole-N,N,N',N'-tetramethyluronium tetrafluoroboric acid (TBTU) and other benzo The use of azole organic condensing agents has provided great help for the research of cyclic peptide synthesis methods; but so far, it has been mainly used in the synthesis of RGD cyclic peptides (cyclic peptides containing arginine-glycine-aspartic acid) ( Wang Xiping. RGD synthesis and preparation process. CN, 103588863B[P]. 6 , especially the reports on related processes of its chemical preparation method

Method used

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  • Preparation method for uniform cyclic peptide Cyclo-(Cys)6
  • Preparation method for uniform cyclic peptide Cyclo-(Cys)6

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Experimental program
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Effect test

Embodiment 1

[0028] A homocyclic peptide Cyclo-(Cys) 6 preparation methods, including:

[0029]Step 1. Soak the 2-chlorotrityl chloride resin in dichloromethane and shake for 30 minutes; remove the solvent after the resin is swollen, and take the amino group with fluorenyl moxycarbonyl protecting group and the side chain mercapto group with trityl protecting group A three-fold molar excess of cysteine ​​was added to the resin, and a ten-fold excess of N,N-diisopropylethylamine was added to the resin, then DMF was added to dissolve it, and the reaction was shaken at room temperature for 30 minutes; then methanol was added to incubate for 20 minutes; Seal the reactive sites on the resin; wash the resin repeatedly with DMF and methanol solvent and remove the solvent, the first amino acid is connected to the resin; after removing the solvent, add a lysate to remove the protecting group on the cysteine ​​amino group Fluorenylmethoxycarbonyl: Take a few resins, wash them thoroughly with ethanol...

Embodiment 2

[0034] A homocyclic peptide Cyclo-(Cys) 6 preparation methods, including:

[0035] Step 1. Soak the 2-chlorotrityl chloride resin in dichloromethane and shake for 30 minutes; remove the solvent after the resin is swollen, and take the amino group with fluorenyl moxycarbonyl protecting group and the side chain mercapto group with trityl protecting group A three-fold molar excess of cysteine ​​was added to the resin, and a ten-fold excess of N,N-diisopropylethylamine was added to the resin, then DMF was added to dissolve it, and the reaction was shaken at room temperature for 30 minutes; then methanol was added to incubate for 20 minutes; Wash the resin repeatedly with DMF and methanol solvent and remove the solvent. The first amino acid is connected to the resin; After fully washing with ethanol, add one drop each of 5% ninhydrin ethanol solution, 0.3% ascorbic acid solution, and 60% phenol solution, and heat to 110°C for 5 minutes at the same time. If the color of the resin t...

Embodiment 3

[0040] A homocyclic peptide Cyclo-(Cys) 6 preparation methods, including:

[0041] Step 1. Soak the 2-chlorotrityl chloride resin in dichloromethane and shake for 30 minutes; remove the solvent after the resin is swollen, and take the amino group with fluorenyl moxycarbonyl protecting group and the side chain mercapto group with trityl protecting group A three-fold molar excess of cysteine ​​was added to the resin, and a ten-fold excess of N,N-diisopropylethylamine was added to the resin, then DMF was added to dissolve it, and the reaction was shaken at room temperature for 30 minutes; then methanol was added to incubate for 20 minutes; Wash the resin repeatedly with DMF and methanol solvent and remove the solvent. The first amino acid is connected to the resin; After fully washing with ethanol, add one drop each of 5% ninhydrin ethanol solution, 0.3% ascorbic acid solution, and 60% phenol solution, and heat to 110°C for 5 minutes at the same time. If the color of the resin t...

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Abstract

The invention discloses a preparation method for uniform cyclic peptide Cyclo-(Cys)6. The method comprises the following steps: (1) connecting resin with cysteine with protecting group through reaction, thereby forming the resin connected with cysteine; (2) continuously condensing the cysteine connected with the resin and the cysteine with protecting group, thereby forming the resin connected with linear chain peptide; (3) cutting the linear chain peptide off from the resin, connecting end to end and cycling, thereby acquiring a crude product of cyclic peptide; (4) purifying and storing the cyclic peptide. The Cyclo-(Cys)6 prepared according to the invention is of a uniform cyclic peptide structure formed by single amino acid and has the structure similar to the structure of crown ether compound; the molecule structurally has excellent regularity and multidirectional symmetry; the cyclic peptide is easier to be self-assembled into an ion channel or a nanometer tube, so as to be used as a drug carrier, a membrane channel and a molecular device; a side chain contains a plurality of sulfydryl functional groups, so that the cyclic peptide has higher reaction activity and can be used as a precursor reagent for efficient click reaction; and meanwhile, the process is reasonable, the operation is simple and convenient and the compounding efficiency is higher.

Description

technical field [0001] The invention belongs to the technical field of polypeptide synthesis, and relates to a solid-phase chemical preparation method of cyclic peptide compounds, in particular to the cyclic peptide compound cyclic peptide Cyclo-(Cys) 6 and its synthetic preparation process. Background technique [0002] Cyclic peptides have a high structural similarity with ordinary chain peptides in terms of structural composition, but because the amino acid residues in the main structure participate in the connection to form a ring, the free carboxyl, amino and other hydrophilic groups in the molecule disappear or decrease. It reduces its polarity, enhances its fat solubility, reduces its sensitivity to ammonia / carboxypeptidase in vivo, and increases its stability in vivo; at the same time, the degree of freedom of peptide chain movement decreases, and it has a relatively stable and definite conformation in solution. The probability of fitting with the receptor is signif...

Claims

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Application Information

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IPC IPC(8): C07K7/64C07K1/06C07K1/04C07K1/16
CPCC07K7/64Y02P20/54Y02P20/55
Inventor 宋宏涛张雅婷安友黄玮
Owner INST OF NUCLEAR PHYSICS & CHEM CHINA ACADEMY OF
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