Glucagon-like peptide-1 fragment analog and application thereof

A technology for glucagon and analogs, which is applied in the field of glucagon-like peptide-1 fragment analogs, can solve the problems of short biological half-life, limited clinical application, and low product purity, and achieve short synthesis cycle and crude product Ease of purification and high yield

Active Publication Date: 2019-05-07
JIAXING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] However, natural GLP-1 has obvious defects: (1) it is easily biodegraded by plasma protease in the body and rapidly filtered and metabolized by the kidneys, and its biological half-life is extremely short, Only 1 to 2 minutes, limited clinical application
(2) The GLP-1 peptide chain is long, the synthesis is difficult, and the product purity is low

Method used

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  • Glucagon-like peptide-1 fragment analog and application thereof
  • Glucagon-like peptide-1 fragment analog and application thereof
  • Glucagon-like peptide-1 fragment analog and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH 2 ; Microwave-promoted solid-phase synthesis of (SEQ.ID NO.1)

[0065] (1) Swelling of the resin

[0066] Weigh 50 mg of Fmoc-Rink amide-MBHAResin (substitution amount 0.4 mmol / g), swell with 7 mL of DCM for 30 min, remove DCM by suction filtration, then swell with 10 mL of NMP for 30 min, and finally rinse with NMP, DCM, and 7 mL of NMP respectively.

[0067] (2) Microwave promotes removal of Fmoc protecting group

[0068] 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...

Embodiment 2

[0083] Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-COOH; (SEQ.ID NO.2)

[0084] The theoretical relative molecular mass is 1088.3. ESI-MS m / z:found[M+2H] 2+ 545.6;calu[M+2H] 2+ 545.1.

Embodiment 3

[0086] Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Lys-Lys-Lys-NH 2 ; (SEQ.ID NO.3)

[0087] The theoretical relative molecular mass is 1473.9. ESI-MS m / z:found[M+2H] 2+ 737.9, [M+3H] 3+ 492.2;calu[M+2H] 2+ 737.9, [M+3H] 3+ 492.3.

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Abstract

The present invention discloses a glucagon-like peptide-1 (GLP-1) fragment analog having a weight-reducing and hypoglycemic activity, or a pharmaceutically acceptable salt thereof, and a sequence is represented by the following general formula (I). A microwave-assisted Fmoc / tBu orthogonal protection solid phase synthesis strategy is used to efficiently and rapidly synthesize the above target compound. The prepared GLP-1 fragment analog has a novel structure and is suitable as an active ingredient of a drug for treating diabetes and obesity. The GLP-1 fragment analog prepared by using the provided microwave-assisted solid phase synthesis technology is high in yield and short in synthesis period, the crude product is easy for purification, and the GLP-1 fragment analog is low in production cost and easy for industrial automation production. Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-X1-X2(I).

Description

technical field [0001] The invention relates to a glucagon-like peptide-1 fragment analog with weight loss and hypoglycemic activity, a synthesis method and application thereof, and belongs to the technical field of glucagon-like peptide-1 fragment analogs. Background technique [0002] With the improvement of living standards, overweight and obesity are on the rise worldwide and have become the fifth leading risk factor for global death, causing at least 2.8 million adult deaths each year. Although the adult obesity rate in China is low, the number of absolute obesity has jumped to the first place in the world. Excessive obesity can lead to various complications such as type 2 diabetes, cardiovascular disease, and dyslipidemia. Among them, obesity combined with diabetes, that is, "obese type 2 diabetes" is gradually becoming popular. [0003] At present, drugs used clinically to reduce the weight of obese patients with type 2 diabetes include lorcaserin, phentermine / topira...

Claims

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Application Information

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IPC IPC(8): C07K14/605C07K1/06A61K38/26A61P3/04A61P3/10
CPCY02P20/55
Inventor 孙李丹沈慧裘远飞黄文龙钱海丁宝月黄越燕黄嬛
Owner JIAXING UNIV
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