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Long-acting polymer drug technique in protein engineering

A technology of protein engineering and multimer, applied in the preparation method of peptides, hybrid peptides, organic chemistry, etc., to achieve long half-life, high local biological activity, and increase the effect of toxic and side effects

Inactive Publication Date: 2010-11-03
北京万达因生物医学技术有限责任公司
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Problems solved by technology

my country has also carried out research on PEG modification of proteins such as IFN and G-CSF, but none of them has been listed yet

Method used

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  • Long-acting polymer drug technique in protein engineering

Examples

Experimental program
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Embodiment

[0046] Example: Long-acting human interferon alpha-1b fusion dimer

[0047] Interferon is an important class of cytokines. It is a group of low-molecular-weight glycoproteins with similar structures and functions produced by immune cells in response to antiviral responses when the body is infected by viruses. Interferon has broad-spectrum anti-virus, anti-cell division, immune regulation and other biological activities on the same type of cells, and is currently widely used in clinical anti-virus and anti-tumor therapy. According to the molecular structure and antigenicity of human interferon, it is divided into α, β, γ and other categories. The active molecule of interferon beta is a dimer, the active molecule of gamma interferon is a tetramer, and the active molecule of natural alpha interferon is still As a monomer, α-interferon is further divided into α-1b, α-2a, α-2b and other subtypes according to its structure.

[0048] Interferon is the first genetically engineered dr...

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Abstract

The invention discloses a long-acting polymer drug technique in protein engineering, which relates to techniques for oligomerizing active protein polypeptide drugs and forming oligomer macromolecules from drug monomers to enhance the drug effect. The invention is characterized in that the active protein polypeptide natural amino acid sequence is connected with the amino acid sequence recombinant protein in the oligomerization domains through flexibly connected short peptides, and the ectopic expression recombinant proteins are polymerized in the oligomerization domains to form a long-acting protein drug in a dimer or tetramer structure. The oligomerization domains are a sort of short amino acid domains which are cross-linked among the natural oligomerized protein monomers, including Van der Waals force formed among monomers, hydrophobic bonds, electrovalent bonds, hydrogen bonds, disufide covalent bonds, domain swapping and other oligomerization domains. The splicing and recombination PCR technique is used for constructing the recombinant genes formed by connecting protein polypeptides with the oligomerization domains; and protocaryon or eukaryon expression protein polypeptide monomers are cross-linked into oligomers through the oligomerization domains. The adenovirus or vaccine carrier system directly expresses the long-acting recombinant drug in vivo.

Description

Technical field: [0001] The invention belongs to the field of biology and medicine-protein engineering drugs, and relates to a technology for developing long-acting multimer protein polypeptide drugs transformed by genetic engineering. Background technique: [0002] The world's first biotech pharmaceutical company was established in 1971. In the early 1980s, a large number of protein and polypeptide bioengineering drugs developed through recombinant DNA technology, represented by interferon and human growth hormone, provided effective treatments for some intractable human diseases. After more than 30 years of rapid development, protein and peptide drugs have become one of the most important types of drugs in the international pharmaceutical market. Compared with chemically synthesized drugs, protein polypeptide drugs have the characteristics of less toxic and side effects, less dosage, and better curative effect. According to reports from abroad, since 2005, the total sale...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00C07K1/10
Inventor 江洪
Owner 北京万达因生物医学技术有限责任公司
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