Agent targeting double-membrane organelle DNA

A technology of bilayer membranes and organelles, applied in the field of complexes of low molecular weight compounds

Pending Publication Date: 2021-12-31
JUNTENDO EDUCATIONAL FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Furthermore, although it has been reported that fat-soluble cationic complexes may affect plant cells and penetrate into chloroplasts (Non-Patent Documents 4 and 5), it has not actually been clarified that low-molecular-weight Complexes of compounds are able to penetrate into the living cells of the plant's roots or leaves, but have also been clearly identified for use in plant

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  • Agent targeting double-membrane organelle DNA
  • Agent targeting double-membrane organelle DNA
  • Agent targeting double-membrane organelle DNA

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preparation example Construction

[0220] The invention provides a complex of a DNA-binding compound that binds to the specific sequence of DNA of a double-membrane structure organelle such as mitochondria and a compound that is localized to a double-membrane structure organelle, and a design and synthesis method thereof. This complex acts on the DNA of double-membrane organelles such as mitochondria, resulting in the reduction of the copy number of double-membrane organelles such as mitochondria with specific sequences that change the function of double-membrane organelles, such as mitochondria, etc. The insufficiency of the membrane-structured organelles induces cell death, etc., thereby enabling the prevention, treatment, and diagnosis of pathologies related to double-membrane structure organelles such as mitochondria.

[0221] Double-membrane organelles include chloroplasts and the like in addition to mitochondria.

[0222] Specific sequences of DNA in double-membrane organelles include mitochondrial DNA se...

Embodiment 1

[0301] Double-stranded membrane structure organelle Double-stranded DNA exists in the small organs of eukaryotic organisms including animals and plants, such as mitochondria or chloroplasts, and is closely related to the energy production of these organisms such as respiration or photosynthesis, and also has physiological functions with active oxygen, etc. The action is related to the production of substances with pathological effects. Moreover, since it is DNA that exists in the cytoplasm and outside the nuclear membrane, it is more susceptible to damage and more likely to accumulate new mutations than DNA in the nucleus. Mutations accumulate with age, and in adult somatic cells In the middle, it becomes a state called "heterogeneity" in which mutant mtDNA and normal mtDNA are mixed. In addition, when the ratio of the mutant mtDNA exceeds a certain level, the function of mitochondria decreases, which causes mitochondrial diseases and the like. It is also known that mtDNA mut...

Embodiment 2

[0401] synthetic lethal experiment

[0402] Before the experiment, whether CCC021-TPP localized to mitochondria was investigated by immunostaining using MitoTrackerRED and anti-TPP antibody in cultured cell lines A549 and PC14. In a 35mm glass-bottom culture dish (Iwaki, Ikuoka) with 5 × 10 3 Inoculate A549 cells in the way of cells / dish at 1×10 4 PC14 cells were seeded in cells / dish, and treated with CCC021-TPP at a final concentration of 20 μM after 24 hours of culture. Then, after 24 hours, the culture solution was removed, and a DMEM culture solution containing MitoTracker (registered trademark) Red CMXRos (Life Technologies, USA) was added so as to become 100 nM. After 30 minutes, the culture medium was washed twice with PBS, and then washed with 4% PFA. After fixing for 30 minutes, they were stored at 4° C. instead of PBS, immunostained with antibodies by the method described in Example 1, and observed with a confocal laser microscope SP8 (Leica, Germany). As a result...

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Abstract

The present invention provides a medicine for pathological conditions including mitochondrial diseases, said medicine comprising a complex of a compound recognizing a double-membrane organelle DNA sequence and a compound localized in double-membrane organelles. A complex wherein a lipid-soluble cation localized in double-membrane organelles is bonded to a linear PI polyamide specifically binding to a double-membrane organelle DNA sequence; a linear PI polyamide-TPP complex targeting a mitochondrial DNA mutation or polymorphism, said complex comprising the aforesaid complex; and a medicinal composition comprising the complex.

Description

technical field [0001] The present invention relates to a complex of low molecular weight compounds targeting double membrane structure organelle DNA. Background technique [0002] Lipid-soluble cations and the like have been developed as a technology for delivering drugs to double-membrane organelles such as mitochondria and chloroplasts (Non-Patent Document 1), and attempts to apply them to the treatment of mitochondria-related diseases have been attempted (Patent Documents 2 to 5). On the other hand, it has also been confirmed that gene mutations in mitochondrial DNA accumulate not only in mitochondrial diseases but also in lifestyle-related diseases and cancerous sites. It has also been reported that the transcription of mitochondrial genes can be regulated by targeting mitochondrial DNA sequences (Non-Patent Document 2), and it has also been reported that it is possible to reduce The number of mitochondria with disease-causing gene sequences (Patent Document 1). Howev...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K47/26A61K47/24A61P35/00A61P43/00C12Q1/6883C12Q1/6886C12N15/11G01N33/53
CPCA61P35/00A61P43/00C12Q1/6886C12Q2600/156G01N33/5079A61K45/06A61K31/787A61K47/54A61K2300/00A61K31/4178
Inventor 永濑浩喜渡部隆义越川信子安井七海
Owner JUNTENDO EDUCATIONAL FOUND
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