Oxyntomodulin (OXM) analogue and application thereof

A technology of oxyntomodulin and analogs, applied in hormone peptides, drug combinations, peptide-nucleic acid and other directions, can solve the problem of weak hypoglycemic activity, achieve balanced hypoglycemic and weight loss activities, short synthesis cycle, and save costs Effect

Inactive Publication Date: 2017-07-28
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 better effects in intervening body weight, regulating lipid metabolism, and improving glucose tolerance, but its hypoglycemic activity is relatively weak

Method used

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  • Oxyntomodulin (OXM) analogue and application thereof
  • Oxyntomodulin (OXM) analogue and application thereof
  • Oxyntomodulin (OXM) analogue and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser-Arg-Arg-Ala-Gln-Asp-Phe-Val-Gln-Trp- Leu-Met-Asn-Thr-Lys-Arg-Asn-Arg-NH 2 (SEQ. ID NO: 2);

[0046] solid phase synthesis

[0047] (1) Swelling of the resin

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

[0049] (2) 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, and react in the solid-state reactor for 1min, the reaction temperature is controlled within 50°C, and the Compress the air with the compressor to cool, and filter the solution after the reaction; then add 7 mL of 25% piperidine / NMP (V / V) solution containing 0.1M HOBt, and react in a solid-phase reactor for another 4 min, and the reaction tempera...

Embodiment 2～9

[0060] According to the method described in Example 1, the oxyntomodulin (OXM) analogs of Examples 2-9 were synthesized according to the corresponding sequences, and their respective molecular weights were confirmed by electrospray mass spectrometry (ESI-MS).

Embodiment 2

[0062] His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser-Arg-Arg-Ala-Gln-Asp-Phe-Val-Gln-Trp- Leu-Met-Asn-Thr-Val-Lys-Gly-Arg-NH 2 (SEQ. ID NO: 3);

[0063] The theoretical relative molecular mass is 3922.4. ESI-MS m / z: found[M+3H] 3+ 1308.5, [M+4H] 4+ 981.5; calc.

[0064] [M+3H] 3+ 1308.4, [M+4H] 4+ 771.2.

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PUM

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Abstract

The invention relates to a novel oxyntomodulin (OXM) analogue and a synthesis method thereof. A terminal C of natural OXM is subjected to Ex-4, GLP-1 and Lixisenatide partial terminal C peptide sequence substitution to obtain the OXM analogue with optimal pharmacological activity, synthesis of a peptide chain is rapidly implemented by an orthogonal protection strategy solid phase synthesis method, a coarse product is purified and freeze-dried to obtain the OXM analogue.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to oxyntomodulin (OXM) analogs and applications 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] Glucagon-like peptide-1 (GLP-1) is a glucose-dependent incretin hormone. It can stimulate the GLP-1 receptor (GLP-1R) and play a hypoglycemic effect. The most notable function is to promote the regeneration and repair of β-cells, increase the number of β-cells in the pancreas, and at the same time avoid the risk of hypoglycemia that often occurs in diabetes treatment. It has broad application prospects in the field of diabetes treatment. [0004] Glucagon (GCG) ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/00C07K1/04C07K1/06C07K1/02A61K38/17A61P3/10A61P3/04
CPCC07K14/001A61K38/00C07K14/605
Inventor 黄文龙钱海蔡星光周洁李杰明廖晨孙李丹
Owner CHINA PHARM UNIV
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