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Micro-assisted solid-phase synthesis of analogue of MC-JJ0101 polypeptide isolated from Momordica charantia and application of the analogue

A MC-JJ0101, solid-phase synthesis technology, applied in the direction of peptides, drug combinations, peptide preparation methods, etc., can solve the problems of inability to synthesize target peptides, loss of meaning of synthesis, long synthesis cycle, etc., to achieve easy industrial automation production, The effect of low production cost and short synthesis cycle

Inactive Publication Date: 2010-09-08
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Using the traditional solid-phase method to synthesize long peptides, the yield is often very low and the impurities are more difficult to purify, thus losing the meaning of synthesis from a practical point of view
Secondly, the synthesis cycle is long. In the case of no difficult peptide sequence in the middle, it usually takes nearly a week to complete the synthesis cycle of 10 peptides. If there is a difficult peptide sequence, it is often impossible to synthesize the target peptide.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Pro-Ala-Gly-Ala-Ala-Ser-Ile-Ser-Ala-Ser (SEQ.ID NO: 2) microwave promoted solid-phase synthesis

[0024] (1) Swelling of resin

[0025] Weigh 50mg of Fmoc-rink amide-MBHA Resin (substitution amount 0.4mmol / g), swell with 7mL DCM for 30min, filter to remove DCM, then swell with 10mL NMP for 30min, and finally rinse with NMP, DCM, NMP 7mL respectively.

[0026] (2) Microwave promotes the removal of Fmoc protecting group

[0027] Put the swollen resin into the reactor, add 7 mL of 25% piperidine / NMP(V / V) solution containing 0.1M HOBT, and react in a microwave reactor for 1 min. The microwave power is 15W and the reaction temperature is controlled at 50°C. Use an air compressor to compress the air for cooling. After the reaction is completed, filter the solution; then add 7mL of 25% piperidine / NMP(V / V) solution containing 0.1M HOBT and react for another 4min in the microwave reactor with a microwave power of 25W , The reaction temperature is controlled at 50°C, and the air compres...

Embodiment 2

[0042] Pro-Ala-Gly-Ala-Ala-Ser-Ile-Lys-Gly-Ser (SEQ. ID NO: 3); Theoretical relative molecular mass is 858.0

[0043] ESI-MSm / z:found[M+3H] 3+ 287.1, [M+4H] 4+ 215.6, [M+5H] 5+ 172.5; calu[M+3H] 3+ 287.0, [M+4H] 4+ 215.5, [M+5H] 5+ 172.6

Embodiment 3

[0045] Pro-Ala-Gly-Ala-Ala-Ser-Ile-Lys-Cys-Ser (SEQ. ID NO: 4); Theoretical relative molecular mass 904.0

[0046] ESI-MSm / z:found[M+3H] 3+ 302.3, [M+4H] 4+ 227.2, [M+5H] 5+ 181.6; calu[M+3H] 3+ 302.3, [M+4H] 4+ 227.0, [M+5H] 5+ 181.8

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PUM

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Abstract

The invention relates to a novel, high-efficiency and blood sugar-lowering analogue of MC-JJ0101 polypeptide isolated from Momordica charantia and a micro-assisted solid-phase synthesis method thereof. The analogue of the MC-JJ0101 polypeptide with longer pharmacologic action time is obtained by modifying positions 2, 4, 5, 8 or 9 of a polypeptide of natural Momordica charantia; the chemical synthesis of the analogue can be efficiently and quickly realized by the micro-assisted solid-phase synthesis method, wherein the analogue of the MC- JJ0101 polypeptide is obtained by purifying a crude product with a preparative high-efficiency liquid phase and freeze-drying the purified product.

Description

Technical field [0001] The invention relates to MC-JJ0101 polypeptide analogs and a microwave-promoted solid-phase synthesis method thereof. Background technique [0002] Diabetes is an important disease endangering human health. At present, about 5%-7% of people in the world suffer from diabetes. It is considered to be the third killer of human disability and death after cardiovascular and cerebrovascular diseases and malignant tumors. . [0003] Diabetes is divided into type I and type II. Type I diabetes is an autoimmune disease. Insulin injection is required for the survival of patients. Type II diabetes accounts for about 95% of the total number of diabetic patients. Type II diabetes is caused by disorders of pancreatic islet cell metabolism, insufficient insulin secretion, or insulin resistance, which is a metabolic disease caused by insulin resistance and relatively insufficient insulin secretion, or relatively insufficient insulin secretion and insulin resistance. Insuff...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06C07K1/20C07K1/08C07K1/06C07K1/04A61K38/08A61P3/10
Inventor 黄文龙金晶钱海张惠斌王敬杰陈巍曹金明戴冬艳
Owner CHINA PHARM UNIV
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