Long-acting oxyntomodulin (OXM) hybrid peptide as well as preparation method and application thereof

A compound and amino acid technology, applied in the field of long-acting gastric oxyntomodulin hybrid peptide, can solve the problems of weak hypoglycemic activity and short half-life, and achieve weight loss, low cost, and cost saving effects

Active Publication Date: 2018-12-07
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Compared with pure GLP-1R agonists, OXM has a better effect in intervening body weight, regulating lipid metabolism, and improving glucose tolerance, but its hypoglycemic activity is relatively weak and its half-life is short

Method used

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  • Long-acting oxyntomodulin (OXM) hybrid peptide as well as preparation method and application thereof
  • Long-acting oxyntomodulin (OXM) hybrid peptide as well as preparation method and application thereof
  • Long-acting oxyntomodulin (OXM) hybrid peptide as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0083]

[0084] solid phase synthesis

[0085] 1, the synthesis of formula I

[0086]Weigh 100mg of 2-CTC resin (degree of substitution: 0.8mmol / g), swell with DCM for 30min, then swell with 10mL of NMP for 30min, rinse with NMP and 7mL of DCM respectively. Fmoc-AEEA (61.6 mg, 0.16 mmol), HBTU (60.6 mg, 0.16 mmol), DIEA (55.6 μL, 0.32 mmol), HOBt (21.6 mg, 0.16 mmol) were dissolved in NMP 10 mL, and this solution was added to the resin After reacting for 2 hours, the reaction solution was filtered off, and 10 mL of DCM:methanol:DIEA 5:4:1 solution was added to the resin to block the reaction for 1 hour, the reaction solution was filtered off, and the resin was washed 3 times with 7 mL each of DCM and NMP.

[0087] Add 25% piperidine / NMP (V / V) solution containing 0.1M HOBt to the resin to remove Fmoc, and wash with NMP after the reaction. In the same way, Fmoc-AEEA was coupled again. After the reaction, the resin was washed 3 times with 7 mL each of DCM and NMP. Add 25% p...

Embodiment 2

[0103]

[0104] The synthesis method was the same as in Example 1, and the collected solution was lyophilized to obtain 26.4 mg of the pure product. The theoretical relative molecular mass is 5010.6. ESI-MS m / z: Calcd.[M+3H] 3+ 1671.2, [M+4H] 4+ 1253.7; Found[M+3H] 3+ 1671.8, [M+4H] 4+ 1253.1.

Embodiment 3

[0106]

[0107] The synthesis method was the same as in Example 1, and the collected solution was lyophilized to obtain 24.2 mg of the pure product. The theoretical relative molecular mass is 4969.5. ESI-MS m / z: Calcd.[M+3H] 3+ 1657.5, [M+4H] 4+ 1243.4; Found[M+3H] 3+ 1657.3, [M+4H] 4+ 1243.7.

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Abstract

The invention relates to a class of long-acting oxyntomodulin (OXM) hybrid peptides as well as application and synthetic methods of the hybrid peptides. The preparation method comprises the followingsteps: modifying the OXM, hybridizing with a peptide sequence of Exenatide, and conjugating fatty acid chains, thereby obtaining the OXM hybrid peptides with long pharmacologic action time and excellent weight losing effects. Synthesis of target polypeptides is rapidly realized by an orthogonal protection strategy solid-phase synthesis method, and the crude product is purified and freeze-dried soas to obtain the target compound.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to long-acting oxyntomodulin (OXM) hybrid peptide and application thereof. Background technique [0002] The cause of metabolic syndrome is abnormal metabolism of various substances such as protein, fat and carbohydrates. Overnutrition and reduced physical activity can lead to obesity and obesity-related diseases such as diabetes. In recent years, the incidence of type 2 diabetes and dyslipidemia has been increasing day by day. [0003] Oxyntomodulin (OXM) is a polypeptide composed of 37 amino acids secreted by small intestinal L cells, including the entire 29 amino acid sequence of glucagon and the 8 amino acid part of the C-terminal extension, which is similar to glucagon Peptide-1 (GLP-1) has 50% homology, and the peptide sequence is: HSQGTFTSDYSKYLDSRRAQDFVQWLMNTKRNRNNIA. OXM can simultaneously activate glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR),...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00A61K38/22A61K38/26A61P3/10A61P3/04A61P3/06A61P1/16
CPCA61K38/00A61P1/16A61P3/04A61P3/06A61P3/10C07K14/57563C07K14/605C07K2319/00A61K47/542
Inventor 钱海黄文龙蔡星光刘春霞李久辉戴雨轩李承业
Owner CHINA PHARM UNIV
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