Nonsense mutation read-through activity application of 3,3'-bis-indolymethane

A diindolylmethane, nonsense technology, applied in the field of biomedicine, can solve the problems of high toxicity, low read-through efficiency, few types of non-sense mutation read-through agents and the like

Inactive Publication Date: 2019-05-14
WUHAN UNIV OF SCI & TECH
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Problems solved by technology

[0005] In view of the problems of the existing nonsense mutation read-through agents such as few types, high toxicity, and l...

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  • Nonsense mutation read-through activity application of 3,3'-bis-indolymethane
  • Nonsense mutation read-through activity application of 3,3'-bis-indolymethane
  • Nonsense mutation read-through activity application of 3,3'-bis-indolymethane

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Embodiment Construction

[0012] The use of the nonsense mutation read-through activity of 3,3'-diindolylmethane will be described below in combination with extracellular and intracellular experiments and results. 1) Detection of nonsense mutation read-through activity of 3,3'-diindolylmethane in extracellular space by PTT-ELISA method

[0013] First, the nonsense mutation read-through activity of 3,3'-diindolylmethane was detected in extracellular. Using the reported drug G418 with nonsense mutation readthrough activity as a positive control, the nonsense mutation readthrough activity was identified using the PTT-ELISA method based on protein truncation test (PTT). The PTT-ELISA method has high sensitivity and reliability in screening nonsense mutation read-through agents. At present, several compounds with clinical potential have been successfully screened by this method.

[0014] This study uses T7 Quick for PCR DNA Kit (Promega), transcribe and translate the plasmid of the ATM gene cDNA fragment...

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Abstract

The invention discloses a nonsense mutation read-through activity application of 3,3'-bis-indolymethane. Preliminary experimental results show that 3,3'-bis-indolymethane can partially recover expression of luciferase with nonsense mutation in a cell model and can partially recover expression of an ATM gene containing nonsense mutation in the extracellular protein truncation experiment, and is expected to serve as a lead compound; new drugs can be developed through structure transformation and modification, various diseases caused by nonsense mutation are treated. 3,3'-bis-indolymethane has potential medical application.

Description

technical field [0001] The invention belongs to the field of biomedicine, and specifically relates to the use of nonsense mutation read-through activity of 3,3'-diindolylmethane. Background technique [0002] Studies have shown that 30% of the diseases caused by human gene mutations are caused by nonsense mutations. Nonsense mutations can cause stop codons to appear early in the coding region during protein translation, causing peptide chain synthesis to terminate, resulting in non-functional or Insufficient truncated protein. At the same time, the premature stop codon will also prolong the time of mRNA staying in the nucleus, and even through the nonsense-mediated mRNA decay (NMD) pathway, the mRNA is selectively degraded and the encoded protein is lost. Therefore, nonsense mutations can lead to the occurrence of numerous tumor diseases and genetic diseases. Research data show that about 12% of genetic diseases are caused by nonsense mutations, involving more than 1,800 d...

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Application Information

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IPC IPC(8): A61K31/404A61P43/00A61P35/00
Inventor 江高峰许蓓杜柳涛
Owner WUHAN UNIV OF SCI & TECH
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