Recombinant human GLP-1-Fc fusion protein

A GLP-1, fusion protein technology, applied in the biological field, can solve the problems of prolonged action time, prolonged half-life, low homology, etc.

Active Publication Date: 2015-02-04
SYNDEGEN SHANGHAI BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since patients with type 2 diabetes need long-term medication, and GLP-1-Fc has the characteristics of prolonging the half-life, the time of its action in the body is also greatly extended compared with the original GLP-1 molecule. Fusion of antibody Fc fragments may increase the risk of patients producing specific antibodies due to antigenic changes

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  • Recombinant human GLP-1-Fc fusion protein
  • Recombinant human GLP-1-Fc fusion protein
  • Recombinant human GLP-1-Fc fusion protein

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preparation example Construction

[0055] The present invention also provides a method for preparing the recombinant human GLP-1-Fc fusion protein, comprising the following steps:

[0056] 1) Cloning the coding sequence of the recombinant human GLP-1-Fc fusion protein into an expression vector;

[0057] In the preparation method of the recombinant human GLP-1-Fc fusion protein provided by the present invention, the preparation method of the coding sequence of the recombinant human GLP-1-Fc fusion protein is not particularly limited. well-known techniques for preparation; the method for cloning the coding sequence into the expression vector is not particularly limited, and various cloning methods in the art can be used, and the specific method that can be used is as follows: design and expression vector multiple cloning sites at both ends of the coding sequence Corresponding enzyme cutting site, after enzyme cutting, the coding sequence is connected to the expression vector; the expression vector is preferably t...

Embodiment 1

[0071] Coding sequence of recombinant human GLP-1-Fc fusion protein

[0072] 1. Amino acid composition of GLP-1

[0073] Natural GLP-1 and any modified GLP-1 molecules can form fusion proteins by linking different flexible linking peptides with different Fc fragments, such as IgG1, IgG2, IgG3, IgG4 and modified ones. These fusion proteins Both have biological activity and long-term effect.

[0074] The amino acid sequence of native GLP-1 is as follows:

[0075] HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG (SEQ ID No: 25).

[0076] The fusion protein molecule of the present invention is a variant modified on the basis of the original GLP-1 molecule, specifically two variants modified on the basis of the 31 amino acids of the original GLP-1 molecule. Its name and molecule The structures are:

[0077] Molecular name: G1 (1 amino acid modification in the 31 amino acid GLP-1 molecule)

[0078] Modification: Gly8-GLP-1 (7-37), the first amino acid number of the original GLP-1 is 7 (position...

Embodiment 2

[0113] Expression of fusion proteins in CHO-DXB11 cells:

[0114] The different recombinant GLP-1-Fc fusion proteins of the present invention and the coding sequence (SEQ ID No: 18-24) of LY2189265 are cloned into the expression vector sequence containing IRES-DHFR, and the expression vector expresses the fusion under the drive of CMV promoter protein.

[0115] The coding sequence of G1-L1-IgG4 (S228P, L234A, L235A) is shown in SEQ ID No: 18:

[0116] atggagtggtcctgggtgttcctgttctttctgtccgtgaccacaggagtccacagccatggtgaagggacctttaccagtgatgtaagttcttatttggaaggacaagctgccaaggagttcattgcttggctggtgaaaggccgtggaggatccggtggcggttcctctaagtacgggcccccttgccctccttgcccagctcctgaatttgagggcggacccagcgtgttcctgttccccccaaagcccaaggacaccctgatgatcagcagaacccccgaagtgacctgcgtggtggtggacgtgtcccaggaagatcccgaggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcccagagaggaacagttcaacagcacctacagagtggtgtccgtgctgaccgtgctgcaccaggattggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccagcagcatcgaaaagaccatcagcaaggccaagggcc...

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Abstract

The invention relates to the technical field of biology, and particularly, relates to a recombinant human GLP-1-Fc fusion protein and a preparation method and an application thereof. The invention provides the recombinant human GLP-1-Fc fusion protein, wherein the recombinant human GLP-1-Fc fusion protein comprises two structural function regions which are respectively a recombinant GLP-1 fragment and a human immunoglobulin Fc fragment, and the recombinant GLP-1 fragment has the amino acid sequence shown in SEQID No.1. The recombinant human GLP-1-Fc fusion protein provided by the invention has the homology with an original GLP-1 molecule reaching 97%, and still maintains excellent biological activity and zoology activity.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a recombinant human GLP-1-Fc fusion protein and its preparation method and application. Background technique [0002] Recombinant human glucagon-like peptide-1 analog (GLP-1), the polypeptide is composed of 31 amino acids, which can stimulate islet cells to produce insulin, so as to achieve the purpose of controlling blood sugar. Glucagon-like peptide-1 (GLP-1) promotes insulin release, reduces plasma glucagon levels, reduces the rate of gastric emptying, promotes satiety and stimulates islet biosynthesis and β-cell proliferation , can be used for the treatment of type 2 diabetes. Type 2 diabetes is widespread in our country. If it is not treated in time, it will easily transform into type 1 diabetes, which will cause a great burden to patients and the country. Therefore, the demand for developing such drugs is extremely urgent. [0003] The currently commercialized GLP-1 drugs inc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00C12N15/62C12N5/10C12N15/63A61K39/395A61K38/26A61P35/00G01N33/68
Inventor 许必雄郭颀然冯金梦
Owner SYNDEGEN SHANGHAI BIOTECH
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