Long-acting broad-spectrum chemotactic factor receptor inhibiting matter

A chemokine receptor and inhibitor technology, applied in the field of chimeric protein compounds, can solve the problems of unselectable inhibition range, specificity but not broad spectrum, instability, etc.

Inactive Publication Date: 2003-08-13
龚小迪
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] The main purpose of the present invention is that in view of the problem that currently developed compounds that inhibit chemokine receptors are either too specific and not broad-spectrum, or too unstable in vivo, several multi-targeted proteins derived from viruses that have been found to inhibit Since the agent is a molecule with a fixed structure, it can neither select the range of inhibition

Method used

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  • Long-acting broad-spectrum chemotactic factor receptor inhibiting matter
  • Long-acting broad-spectrum chemotactic factor receptor inhibiting matter
  • Long-acting broad-spectrum chemotactic factor receptor inhibiting matter

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Embodiment 12

[0084] The application of the long-acting broad-spectrum chemokine receptor inhibitor of the present invention:

[0085] The invention includes the use of these chimeric proteins or their gene fragments (DNA, RNA). a). As a drug used in clinical treatment, a large number of published research results have proved that chemokine proteins and their receptors play an important role in the pathological process of many diseases. Studies have also found that many diseases involve a variety of different chemokine receptors. For example, AIDS virus infection, allogeneic organ transplant rejection, metastasis of certain tumor cells, various autoimmune diseases, non-specific inflammatory diseases (see above). There are many other diseases not listed here. The chimeric protein invented here overcomes the diversity and complexity of disease pathology due to its ability to efficiently inhibit a variety of different chemokine receptors. At the same time, because the chimeric protein has a...

Embodiment 1

[0094] In order to facilitate the understanding of the present invention, some specific embodiments of the present invention are listed below. Example 1 Gene Recombination of Chimeric Protein XR4 / R5 / R1

[0095] The cDNAs (including leader sequences) of the chemokines SDF-1 and RANTES were obtained from human tissue RNA by RT-PCR. The cDNA was cloned into PCR2.1 vector. The genetic mutation of the chemokine is used to modify the gene of the chemokine to form another nucleic acid sequence. On the other hand, the cDNA of the heavy chain constant region of human immunoglobulin IgG4 was obtained from the cDNA library of human spleen using the published sequence, and this fragment was inserted into the expression vector (here, a modified pCR3.1 vector pHC, using CMV as a promoter, EU as an enhancer, and neomycin insensitive gene as a selection marker). The 3' ends of the above-mentioned genetically engineered RANTES sequence fragment and the transformed SDF-1 sequence fragment we...

Embodiment 2

[0097] Example 2 Gene Recombination of Chimeric Protein XR4 / R7

[0098] The gene of chemokine MIP-3β was obtained from human tissue cDNA library by PCR method, and cloned into PCR2.1 vector. It is transformed into a new nucleic acid sequence by gene mutation method. On the other hand, the cDNA fragment of the heavy chain constant region of human immunoglobulin IgG1 (obtained from the human spleen cDNA library using the published sequence) was incorporated into the expression vector (the vector pHC was used here, and the CMV is the promoter, EU is the enhancer, and the neomycin insensitive gene is the selection marker). The 3' end of the genetically engineered MIP-3β sequence fragment and the SDF-1 sequence fragment were respectively connected to the 5' end of IgGγ1 through an enzyme cut point. In addition, an expression vector for the constant region fragment of the human immunoglobulin light chain kappa was made, as in Example 1. Example 3 Expression of chimeric protein XR...

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Abstract

A chimeric protein compound for durable and efficient suppression to different chemotactic factor receptors, its nucleic acid sequence, and the process for preparing and testing its products are disclosed. It can be used to prevent and cure HIV infection, tumor transfer, tissue transplant rejection and self immunopathy. Its advantages are high durability, broad spectrum, and high selectivity.

Description

1. Technical field [0001] The present invention relates to chimeric protein compounds, in particular to a long-acting broad-spectrum chemokine receptor inhibitor. 2. Background technology [0002] Studies have found that the protein (Chemokine) of cell chemokines and its receptors play an important role in the pathological process of many diseases: HIV uses the receptors of chemokines to infect the human body, so if these receptors can be blocked , can prevent the infection of HIV; in addition, the transfer of some tumor cells to some specific organs is also completed through the chemokine receptors on the surface of tumor cells; when various non-specific inflammatory diseases occur, there are tendencies Infiltration of leukocytes into lesions mediated by cytokines. Therefore, effectively inhibiting the receptors of chemokines can inhibit cell movement and achieve the effect of treating and preventing non-specific inflammatory diseases and tumor metastasis. [0003] Studie...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61P29/00A61P31/12A61P31/18A61P35/00A61P37/02A61P37/06C07K19/00C12N15/09
Inventor 龚疆红
Owner 龚小迪
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