Novel blood sugar lowing polypeptide and uses thereof

A new type of technology for hypoglycemia, applied in the field of GLP-1 modified peptides, can solve the problems of not obtaining hypoglycemic effect and stability

Active Publication Date: 2007-09-26
ZHUHAI UNITED LAB
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It can be seen that many previous studies have not obtained muc...

Method used

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  • Novel blood sugar lowing polypeptide and uses thereof
  • Novel blood sugar lowing polypeptide and uses thereof
  • Novel blood sugar lowing polypeptide and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027]The present invention modifies the main action site of DDP-IV, the most important factor affecting the stability of GLP-1, that is, the Ala of GLP-1 8 The carboxy-terminal amino acid of NEP 24.11; at the same time, the modification of the enzyme cleavage site of NEP 24.11 has also been studied and analyzed, mainly in GLP-1 (12-15). Using bioinformatics tools such as productprotein protein structure prediction software, Vector NTI DNA and protein sequence analysis software, the GLP-1 similar peptide sequence was screened and analyzed. According to the principle of secondary structure similarity, a set of GLP-1 analogue polypeptide sequences was obtained.

[0028] The primary screening GLP-1 analogs are listed as follows:

[0029] SEQ NO 1

[0030] HAEGTFTSDVSSYLEGQAAK FI wxya

[0031] SEQ NO 2

[0032] HAEGTFTSDVSSYLEGQAAK FI wxya

[0033] SEQ NO 3

[0034] HAEGTFTSDVSSYLEGQAAK FI wxya

[0035] SEQ NO 4

[0036] HAEGTFTSDVSSYLEGQAAK FI wxya

[003...

Embodiment 2

[0102] Embodiment 2: chemically synthesized polypeptide

[0103] One of the polypeptides of the present invention is synthesized by solid-phase synthesis, and the sequence is: HGEGTFTSDLSSYLEGQAAKLFIEWLVKGR-NH 2 (SEQ NO 17), the synthesis method of other polypeptide sequences is similar.

[0104] Synthesis

[0105] Using the Fmoc synthesis method, Rink-Amide-MBHA Resin (purchased from Nankai Hecheng Company) was selected for synthesis. The synthesis steps are as follows:

[0106] 17 kinds of Fmoc-amino acid raw materials with side chain protecting groups——solid phase synthesis——removal of side chain protecting groups——HPLC purification——lyophilization——GLP analogs

[0107] amino acid name

source

Fmoc-L-Ala-OH

Synpep.Inc

[0108] Fmoc-L-Arg(Pme)-OH

Fmoc-L-Asn(Trt)-OH

Fmoc-L-Asp(OtBu)-OH

Fmoc-L-Gln(Trt)-OH

Fmoc-L-Glu(OtBu)-OH

Fmoc-L-Gly-OH

Fmoc-L-His(Trt)-OH

Fmoc-L-Ile-OH

Fmoc-L-Leu-OH

Fmoc-...

Embodiment 3

[0168] Example 3: Research experiments on the hypoglycemic effect of polypeptides

[0169] experiment material:

[0170] 1. Sample:

[0171] SEQ NO 2: HAEGTFTSDVSSYLEGQAAKLFINWLVKGR-NH2

[0172] SEQ NO 5: HAEGTFTSDLSSYLEGQAAKLFIEWLVKGR-NH2

[0173] SEQ NO 6: HAEGTFTSDLSSYLEGQAAKLFINWLVKGR-NH2

[0174] SEQ NO 7: HAEGTFTSDLSSYLEGQAAKSFIEWLVKGR-NH2

[0175] SEQ NO 8: HAEGTFTSDLSSYLEGQAAKSFINWLVKGR-NH2

[0176] SEQ NO 17: HGEGTFTSDLSSYLEGQAAKLFIEWLVKGR-NH2

[0177]SEQ NO 18: HGEGTFTSDLSSYLEGQAAKLFINWLVKGR-NH2

[0178] SEQ NO 33: HVEGTFTSDASSYLEGQAAKLFIEWLVKGR-NH2

[0179] GLP-1(7-36) as positive control: HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR-NH2

[0180] 2. Animals: Wistar rats, male, weighing 280-300 g, provided by the Animal Experiment Center of Jilin University School of Basic Medicine.

[0181] 3. Reagents: ① Blood glucose kit, Zhongsheng Beikong Biotechnology Co., Ltd.; ② Insulin (INS) radioimmunoassay kit, Beijing Furui Bioengineering Company.

[0182] 4. Instrument: ①GF-...

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Abstract

The invention discloses a GLP-1 peptide, whose general formula is HX1EGTFTSDX2SSYLEGQAAKX3FIX4WLVKGR (formula I), wherein X1 is Ala, Gly or Val; X2 is Val, Leu or Ala; X3 is Leu or Ser; X4 is Glu or Asn.

Description

technical field [0001] The present invention relates to human glucagon-like peptide-1 (GLP-1) analogs, specifically the present invention relates to GLP-1 modified polypeptides, which can promote insulin secretion and lower blood sugar in vivo, and can be used to treat type II diabetes. Background technique [0002] According to the report in "Diabetes Atlas" by the International Diabetes Federation (IDE) in 2006, diabetes has spread globally. At present, diabetes affects 246 million people in the world, accounting for 5.9% of the global population, and nearly 80% of the total number of patients are in developing countries, including 40.9 million in India and 39.8 million in China. The report predicts that if no measures are taken in the next two decades, the number of patients with diabetes will increase to 380 million. The prevalence of diabetes in the world and the rapid development of new drugs for treating diabetes will make the market for diabetes drugs increase by 1...

Claims

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Application Information

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IPC IPC(8): C07K14/47A61K38/17A61P3/10
Inventor 肖拥军曹春来陈晓静
Owner ZHUHAI UNITED LAB
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