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chromatin peptide for blocking human HIF-1 alpha gene and regulating network downstream related gene

A chromatin, human technology, applied in the field of preparing drugs for treating tumors

Active Publication Date: 2008-09-17
王成球 +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, for malignant growth of any solid tumor, energy and nutrient constraints must be exceeded

Method used

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  • chromatin peptide for blocking human HIF-1 alpha gene and regulating network downstream related gene
  • chromatin peptide for blocking human HIF-1 alpha gene and regulating network downstream related gene
  • chromatin peptide for blocking human HIF-1 alpha gene and regulating network downstream related gene

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0077] The polypeptide of sequence 1-21 in the sequence listing is synthesized by solid-phase peptide synthesis technique (SPPS), including stepwise addition of amino acids protected with protecting groups to growing oligopeptide chains, which are anchored to chemically stable particles , so that the synthesized peptide can be separated from reagents and solvents by simple filtration. After the synthesis, the chain is cleaved from the carrier and purified.

Embodiment 2

[0079] Chromatin 9 / 10 peptide that blocks the HRE / XRE element of the HIF-1α gene's own promoter and downstream genes of the HIF-1α transcription factor: that is, the Trans-chromatin 10 peptide NH that blocks the HRE element 2 -Lys Arg Lys GluLys Ser Arg Asp Ala Ala Arg-COOH and Cis-chromatin 9 peptides blocking XRE elements: NH 2 -His Ser Glu Ile Glu Arg Arg Arg Arg Arg-COOH: These two chromatin peptides can selectively close the cellular hypoxia response pathway that cancer cells must go through for malignant proliferation / invasion / metastasis, while normal cells do not need to go through this way. Therefore, they are suitable for inhibiting and preventing the recurrence of the disease commonly seen in advanced cancer patients and surgical patients, and achieving a non-toxic curative effect.

Embodiment 3

[0081] The patient's lung cancer metastasized to the bone marrow. Lung radiation therapy. Other parts because of the wide range. Chromatin 14 peptide Arg Arg LysGlu Lys Ser Arg Asp Ala Ala Arg Ser Arg Arg, which blocks the HRE element of the HIF-1α gene promoter and downstream genes of the HIF-1α transcription factor, was administered intravenously every 5 days starting from the fifth day , 2mg each time, one month as a course of treatment. Antibiotics were used to control the concurrent infection. The symptoms of bone pain were alleviated after 5 days, and the symptoms of bone pain disappeared after 20 days. All tumors disappeared after 3 months.

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Abstract

Disclosed is a category of chromatin peptide medicinal molecules capable of blocking human cell anoxybiotic reaction channels, the molecules are DNA compatible structure domain sequences of the related transcription factors or their bionic molecules or derivatives containing 5-100 amino acid residues, they can be specifically bond to HIF-1 alpha self-promotors or transcription factor driven over 40 downstream gene promotors expressed thereby, the molecules can close the molecular channels for cell anoxybiotic reactions including cell sugar glycolysis reaction and / or immunological inflammation reaction and / or vessel generation reaction, thus closing the non-controlled propagation of late stage cancer cells or chronic inflammation cells under anoxybiotic conditions.

Description

technical field [0001] The invention belongs to the field of human genomics and biological self-treatment approach / technology of malignant tumors. More specifically, the present invention relates to a class of chromatin peptide drug molecules that block the human HIF-1α gene and downstream related genes in the regulatory network, and their use in the preparation of drugs for treating tumors. Chromatin peptide is an oligomeric peptide, which is the degradation product of some transcription factors in organisms, generally containing 5-100aa. They are certain transcription factors and DNA-binding domains / DNA-binding Domain (DNA-binding domain) fragments. [0002] The chromatin peptides referred to in this technology are the degradation products of the transcription factor HIF-1α and the transcription factors related to HIF-1α in the regulatory network and auxiliary proteins and their biomimetic molecules. These chromatin peptides have homologous amino acid sequences, and they I...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/17A61K38/08A61K38/10A61P35/00C07K14/435C07K7/00A61K35/10
CPCC07K14/4703A61K38/1709A61P35/00A61P43/00
Inventor 卞小庄王成球何谧窦德献
Owner 王成球
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