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 analogues, which is applied in the field of MC-JJ6 polypeptide analogues and microwave-promoted solid-phase synthesis, can solve the problems of inability to synthesize target polypeptides, loss of meaning of synthesis, purification of impurities, etc., and achieve convenient purification work , shorten the synthesis cycle, the effect of short synthesis cycle

Inactive Publication Date: 2010-04-07
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-promoted solid-phase synthesis of Lys-Thr-Gly-Met-Lys-His-Met-Ala-Gly-Ala-Ala (SEQ.ID NO: 2)

[0047] (1) Swelling of the resin

[0048] Weigh 50mg of Fmoc-Ala 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, and NMP 7mL respectively.

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

[0050] Put the swollen resin into the reactor, add 7mL of 25% piperidine / NMP (V / V) solution containing 0.1M HOBT, react in the microwave reactor for 1min, the microwave power is 15W, and the reaction temperature is controlled at 50°C Within the time period, use an air compressor to compress the air to cool, and filter the solution after the reaction; add 7 mL of 25% piperidine / NMP (V / V) solution containing 0.1M HOBT and react in a microwave reactor for another 4 minutes, and the microwave power is 25W , the reaction temperature was controlled at 50°C, 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 invention relates to a MC-JJ6 polypeptide analog and a microwave-promoted solid-phase synthesis method thereof. Background technique [0002] Diabetes is an important disease that endangers human health today. At present, about 5%-7% of people in the world suffer from diabetes. It is considered to be the third largest 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 that requires insulin injections for survival. Type II diabetes accounts for about 95% of the total number of diabetic patients. Type II diabetes is caused by metabolic disorders of islet cells, insufficient insulin secretion, or insulin resistance, which is a metabolic disease caused by insulin resistance mainly accompanied by relatively insufficient insulin secretion, or relatively insufficient insulin secretion accompanied by i...

Claims

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Application Information

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Patent Type & Authority Applications(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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