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A F1F0-ATP synthetase RNA inhibitor combined with α subunit and its application

A technology of F1F0-ATP and inhibitors, which is applied in the direction of DNA/RNA fragments, recombinant DNA technology, drug combination, etc., can solve the problems of low specificity and high cytotoxicity, and achieve simple production process, strong specificity, The effect of small fragments

Active Publication Date: 2021-03-02
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The above ATP synthase inhibitors are all chemical compounds, which have the disadvantages of high cytotoxicity and low specificity.

Method used

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  • A F1F0-ATP synthetase RNA inhibitor combined with α subunit and its application
  • A F1F0-ATP synthetase RNA inhibitor combined with α subunit and its application
  • A F1F0-ATP synthetase RNA inhibitor combined with α subunit and its application

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Embodiment Construction

[0029] Further description will be given below in conjunction with the embodiments shown in the accompanying drawings.

[0030] An RNA inhibitor of F1F0-ATP synthase α subunit, the sequence of the inhibitor is:

[0031] 5'-UGGAUGGAGAACUGAUAAGGGU-3';

[0032] The complementary sequence is: 5'-ACCCUUAUCAGUUCUCCAUCCA-3'.

[0033] The preparation method of this inhibitor is as follows:

[0034] 4. Synthetic single strand:

[0035] Use the ABI394 RNA automatic synthesizer to synthesize RNA sequences, and synthesize single-stranded RNA in solid phase: first, input the RNA sequence 5'-UGGAUGGAGAACUGAUAAG GGU-3' to be synthesized into the synthesizer, and chemically synthesize RNA from 3' to 5'. Synthesize as follows:

[0036] 1) deprotection group; use trichloroacetic acid to remove the protective group DMT (dimethoxytrityl) of the nucleotide connected in advance on the CPG to obtain a free 5'-hydroxyl end;

[0037] 2) Activation; the protonated nucleoside 3'-phosphoramidite mon...

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Abstract

The invention relates to an anti-F1FO-ATP synthetase active drug. The purpose is to provide a F1F0‑ATP synthase RNA inhibitor that binds to the α subunit. The inhibitor releases the α subunit from the mitochondrial membrane into the cytoplasm by binding to the F1F0‑ATP synthase α subunit, resulting in the synthesis of F1F0‑ATP Enzymatic depolymerization, thereby reducing the activity of ATP synthase and inhibiting intracellular ATP synthesis, has the characteristics of high inhibition efficiency, convenient synthesis, and low cost. The technical solution is: coaxial cable fatigue detection equipment, characterized in that: a F1F0-ATP synthetase RNA inhibitor (named dsRNA-184-U), characterized in that the sequence of the inhibitor is as follows: 5'-UGGAUGGAGAACUGAUAAGGGU ‑3'.

Description

technical field [0001] The invention relates to an anti-F1F0-ATP synthetase active drug, in particular to an RNA inhibitor that inhibits the ATP synthetase activity by binding to the α subunit of the F1F0-ATP synthetase. Background technique [0002] F1F0-ATP synthase is a multi-subunit transmembrane protein complex. F1 is located in the cytoplasm and contains 3α, 3β, ε, γ and δ subunits. F1F0-ATP synthase can synthesize and hydrolyze ATP (adenosine triphosphate), and regulate the energy supply of organisms. The abnormal expression of ATP is the basis of many diseases. For example, the abnormal expression of ATP is closely related to the abnormal proliferation of fundus blood vessels, myocardial ischemia, malignancy, invasiveness and poor prognosis of tumors; the metastasis and proliferation of tumor cells require more ATP, therefore, can selectively kill tumor cells and inhibit tumor angiogenesis by inhibiting intracellular ATP levels. F1F0-ATP synthetase is the key enzy...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/113C07H21/02C07H1/00A61P35/00A61P27/02A61P31/06A61P37/02A61P9/10
CPCC07H1/00C07H21/02C12N15/113C12N2310/14Y02P20/55
Inventor 罗月球姚克刘思雨
Owner ZHEJIANG UNIV