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Method for solid phase synthesis of bitter gourd MC-JJ6 peptide analogs under microwave irradiation and application of bitter gourd MC-JJ6 peptide analogs

A technology of MC-JJ6 and bitter gourd, which is applied to medical preparations, peptides, and drug combinations containing active ingredients, can solve the problems of inability to synthesize target polypeptides, loss of synthetic significance, and long synthesis cycle, and achieve easy automation, The effect of easy industrial automation production and short synthesis cycle

Inactive Publication Date: 2012-05-09
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

[0046] Microwave-assisted solid-phase synthesis of Lys-Thr-Gly-Met-Lys-His-Met-Ala-Gly-Ala-Ala (SEQ.ID NO: 2)

[0047] (1) Swelling of resin

[0048] Weigh 50 mg of Fmoc-Ala Resin (substitution amount 0.4 mmol / g), swell with 7 mL of DCM for 30 min, filter to remove DCM, swell with 10 mL of NMP for 30 min, and finally rinse with 7 mL of NMP, DCM, and NMP respectively.

[0049] (2) Microwave promotes the removal of Fmoc protecting group

[0050] 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 ℃, and the a...

Embodiment 2

[0064] Gly-Thr-Asn-Met-Lys-Gly-Met-Ala-Gly-Ala-Ala (SEQ. ID NO: 3); Theoretical relative molecular mass 1008.2. ESI-MS m / z: found[M+3H] 3+ 337.1, [M+4H] 4+ 253.0, [M+5H] 5+ 202.6; calu[M+3H] 3+ 337.0, [M+4H] 4+ 253.1, [M+5H] 5+ 202.5;

Embodiment 3

[0066] Ala-Thr-Asn-Met-Lys-Gly-Met-Ala-Gly-Ala-Ala (SEQ. ID NO: 4); Theoretical relative molecular mass 1022.2. ESI-MSm / z: found[M+3H] 3+ 341.7, [M+4H] 4+ 256.6, [M+5H] 5+ 205.4; calu[M+3H] 3+ 341.7, [M+4H] 4+ 256.6, [M+5H] 5+ 205.4;

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PUM

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Abstract

The invention relates to new bitter gourd MC-JJ6 peptide analogs capable of efficiently regulating blood sugar level, and a method for solid phase synthesis of bitter gourd MC-JJ6 peptide analogs under microwave irradiation. The method comprises the following steps: obtaining the MC-JJ6 peptide analogs having longer pharmacological effect time by modifying 2, 4, 5, 8 or 9 site of natural bitter gourd analogs; efficiently and quickly realizing the chemical synthesis of the MC-JJ6 peptide analogs by adopting a solid phase synthesis method under microwave irradiation; purifying the crude products by using preparation grade highly effective liquid phase; and freeze-drying the purified products to obtain the MC-JJ6 peptide analogs.

Description

Technical field [0001] The present invention relates to MC-JJ6 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. I...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/06A61K38/08A61P3/10C07K1/06C07K1/04
Inventor 黄文龙金晶钱海张惠斌王敬杰陈巍陈鑫纪剑峰朱孝云
Owner CHINA PHARM UNIV
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