Method for synthesizing cyclopeptide by multicomponent reaction under enzyme catalysis actions

A multi-component reaction and cyclic peptide technology, applied in fermentation and other directions, can solve problems such as ring formation, and achieve the effects of simple process, high purity, and simple separation and purification

Active Publication Date: 2015-11-25
JIANGSU INST OF NUCLEAR MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The purpose of the present invention is to solve the problem of difficult intermolecular chain extension or intramolecular ring formation in the process of preparing cyclic peptides by multi-component reactions in the prior art, and to provide a method that is catalyzed by enzymes, which is easy to Synthesis of Cyclic Peptides with Intermolecular Chain Extension and Intramolecular Loop Formation

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  • Method for synthesizing cyclopeptide by multicomponent reaction under enzyme catalysis actions
  • Method for synthesizing cyclopeptide by multicomponent reaction under enzyme catalysis actions
  • Method for synthesizing cyclopeptide by multicomponent reaction under enzyme catalysis actions

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Effect test

Embodiment 1

[0034] Chloroform phase: Add 5 ml of chloroform to a 20 ml vial, and ventilate argon for ten minutes to remove the oxygen in the chloroform. Then add 20% of the total mass of the reactants (diamine, isonitrile, aldehyde) of Candida antarctica lipase, 1 mmol of n-butyraldehyde and 1 mmol of 2,2-dimethyl-1 to the solution , 3-propanediamine, and stir at room temperature for 15 minutes. After the reaction solution was completely clear, 1 mmol of ethyl isonitrile was added to the reaction solution, and the reaction solution was stirred at room temperature for 48 hours. After the reaction, the reaction solution is bright yellow clear liquid, the reaction solution is separated from the lipase, and the composition of the reaction solution is directly analyzed by mass spectrometry. The chloroform phase is not purified by HPLC.

[0035] The reaction solution was characterized by mass spectrometry. Among the numerous ion signal peaks, three special signal peaks of 242.2, 483.4 and 724.5...

Embodiment 2

[0038] Aqueous phase: Add 5 ml of water to a 20 ml vial, and argon for ten minutes to remove oxygen in the water. Then add 20% of the total mass of the reactants (diamine, isonitrile, aldehyde) to the solution and add 20% of the total mass of the Candida antarctic lipase, 1 millimole of n-butyraldehyde and 1 millimole of 2,2- Dimethyl-1,3-propanediamine was stirred at room temperature for 15 minutes. After the reaction solution was completely clear, 1 mmol of ethyl isonitrile was added to the reaction solution, and the reaction solution was stirred at room temperature for 48 hours.

[0039] The reaction solution was characterized by mass spectrometry, such as figure 2 As shown, the four regular signal peaks 242.2, 483.4, 724.5 and 965.7 correspond to cyclic peptides of corresponding molecular weights, and there are very few impurity ion peaks.

[0040] The structure and yield of the formed cyclic peptide are shown in Table 1. With mass spectrometry, the product in water is almost...

Embodiment 3

[0042] Chloroform / water mixed phase: Add 5 ml of chloroform / water (volume ratio 1:1) into a 20 ml vial, and let argon gas for ten minutes to remove oxygen in the solution. Then add 20% of the total mass of the reactants (diamine, isonitrile, aldehyde) of Candida antarctica lipase, 1 mmol of n-butyraldehyde and 1 mmol of 2,2-dimethyl-1 to the solution , 3-propanediamine, and stir at room temperature for 15 minutes. After the reaction solution was completely clear, 1 mmol of ethyl isonitrile was added to the reaction solution, and the reaction solution was stirred at room temperature for 48 hours. After the reaction, the water layer of the reaction solution was a bright yellow clear solution, and the chloroform layer was a light yellow clear solution. Separate the reaction solution and lipase, and directly analyze the composition of the aqueous phase and the chloroform phase by mass spectrometry. No HPLC purification.

[0043] The reaction solution was characterized by mass spec...

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Abstract

The invention discloses a method for synthesizing cyclopeptide by multicomponent reaction under enzyme catalysis actions, which comprises the following step: in a liquid-phase system, reacting diamine, isonitrile and aldehyde under the catalytic action of an enzyme to obtain the cyclopeptide. The diamine is introduced into the multicomponent reaction, and is subjected to intermolecular chain extension and intramolecular cyclization under the catalytic action of the enzyme to prepare the cyclopeptide containing different quantities of peptide bond units. The method can efficiently construct the straight-chain peptide molecule without any other catalyst or condensing agent, and implements the synthesis of the cyclopeptide under the action of in-situ induced cyclization; and especially under the action of water, the purity of the generated cyclopeptide is higher than 95%.

Description

Technical field [0001] The invention relates to a method for synthesizing cyclic peptides, in particular to a method for synthesizing cyclic peptides by enzyme-catalyzed multi-component reaction. Background technique [0002] Cyclic peptides have excellent antibacterial, anti-tumor, and anti-immune activities, and can form a restricted conformation. Compared with the corresponding linear peptides, they have better resistance to enzymatic hydrolysis and chemical degradation in vivo. Restricted conformations are called "Privileged Structures" in drug design. Cyclic peptides with restricted conformations also have better specificity and targeting affinity. Therefore, cyclic peptides have been widely used in medicine, materials and other fields. [0003] Since the first cyclic peptide (GramicidinS) was discovered in the 1940s, the synthesis of cyclic peptides usually takes amino acids as raw materials through lactamation, lactonization, ligation reactions, sulfhydryl-thioester exchange...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P17/14C12P21/04
Inventor 严骏杰杨敏潘栋辉徐宇平杨润琳王立振赵富宽张波
Owner JIANGSU INST OF NUCLEAR MEDICINE
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