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Multifunctional variant protein and fusion protein thereof

A fusion protein and receptor protein technology, applied in the field of biomedicine, can solve the problems of inability to effectively achieve blood sugar control, weight loss, and dosage limitation of patients

Pending Publication Date: 2022-02-22
SHANGHAI HANSOH BIOMEDICAL +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the dosage of GLP-1 polypeptide and its derivatives is limited by the side effects caused by it, so its clinical use cannot effectively achieve blood sugar control and weight loss in patients

Method used

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  • Multifunctional variant protein and fusion protein thereof
  • Multifunctional variant protein and fusion protein thereof
  • Multifunctional variant protein and fusion protein thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0136] Preparation of Example 1 Numbering Compound 1

[0137] 1.1 Purpose of the experiment: to prepare No. compound 1 by means of cell expression and purification

[0138] 1.2 Experimental scheme:

[0139] 1.2.1 Main experimental reagents

[0140] name brand Item No. NI Sepharose excel GE 17-3712-01 NaOH Shanghai Examination 10019718 imidazole Shanghai Examination 10000218 PBS Prosperity BF-0012 75% ethanol Shanghai Examination 801769610

[0141] 1.2.2 Main experimental instruments

[0142] name brand model Protein Purifier GE AKTA-Pure150 pipette Eppendorf 100-1000μL pipette Eppendorf 20-200μL pipette Eppendorf 2-20μL Magnetic stirrer Shanghai Meiyingpu H03-A micro spectrophotometer Hangzhou Aosheng Nano-300 balance Sartorius SQP QUINTIX124-1CN / 120 pH meter Mettler FE28 Multifunctional Microplate Reader Thermo Lux

[0...

Embodiment 2

[0149] The preparation of embodiment 2 numbering compound 2-160

[0150] 2.1 Purpose of the experiment: to prepare No. compound 2-160 by means of cell expression and purification

[0151] 2.2 Experimental method: Compound 2-160 was prepared by the method in Example 2.

[0152] 2.3 Experimental results: The concentration and purity of numbered compound 2-160 were determined by ultraviolet spectrophotometry, as shown in the following table:

[0153]

[0154]

[0155]

[0156]

[0157]

Embodiment 3

[0158] The preparation of embodiment 3 numbering compound 168

[0159] 3.1 Purpose of the experiment: Compound No. 168 was prepared by cell expression and purification.

[0160] 3.2 Experimental scheme:

[0161] 3.2.1 Main experimental materials

[0162] name brand Item No. Eshmuno A MERCK 1.25161.0001 NaOH Shanghai Examination 10019718 Acetic acid Shanghai Examination 10000218 Sodium acetate (trihydrate) Shanghai Examination 10018718 PBS Prosperity BF-0012 75% ethanol Shanghai Examination 801769610

[0163] 3.2.2 Main experimental instruments

[0164] name brand model Protein Purifier GE AKTA-Pure150 pipette Eppendorf 100-1000μL pipette Eppendorf 20-200μL pipette Eppendorf 2-20μL Magnetic stirrer Shanghai Meiyingpu H03-A micro spectrophotometer Hangzhou Aosheng Nano-300 balance Sartorius SQP QUINTIX124-1CN / 120 pH meter Mettler ...

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PUM

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Abstract

The invention provides a multifunctional variant protein and a fusion protein thereof, and the multifunctional variant protein comprises Fibroblast growth factor 21(FGF21) protein or a mutant protein thereof and a Glucagon-like peptide-1 (GLP-1) receptor or a mutant protein thereof, wherein the pharmaceutical composition of the fusion protein can be used for treating diabetes, obesity, dyslipidemia, metabolic syndrome, nonalcoholic fatty liver disease, nonalcoholic fatty hepatitis and other related diseases.

Description

technical field [0001] The invention belongs to the field of biomedicine, in particular to a novel mutant protein of fibroblast growth factor 21 (FGF21) and its fusion with a glucagon-like peptide-1 (GLP-1) receptor protein, and can be used to treat diabetes, obesity, dyslipidemia, metabolic syndrome, non-alcoholic fatty liver or non-alcoholic steatohepatitis and other related diseases. Background technique [0002] Fibroblast growth factor 21 (Fibroblast growth factor 21, FGF21) is a polypeptide (SEQ ID NO: 166) consisting of 209 amino acids, and its amino acid sequence has about 75% homology with mouse FGF21. The FGF21 N-terminal contains a signal peptide consisting of 28 amino acids, so mature FGF21 consists of 181 amino acids (SEQ ID NO: 167). FGF21 is mainly expressed in the liver and pancreas, but also in fat and muscle tissue. Through the mediation of FCFR and the assistance of the transmembrane protein βKlotho (KLB), FGF21 can induce various signaling pathways and ...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N15/62A61K38/18A61K38/17A61P3/10A61P3/04A61P3/06A61P3/00A61P1/16
CPCC07K14/50C07K14/72A61P3/10A61P3/04A61P3/06A61P3/00A61P1/16C07K2319/00C07K2319/30A61K38/00
Inventor 余华星花海清包如迪
Owner SHANGHAI HANSOH BIOMEDICAL
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