Small peptide TAT-AVPY for treating ischemic brain damage, and application thereof

A TAT-AVPY, ischemic brain injury technology, applied in the medical field, can solve problems such as reducing the activation of caspase-3, and achieve the effects of reducing apoptosis, reducing activation, and facilitating drug delivery

Inactive Publication Date: 2016-07-20
许铁
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The study found that giving the caspase-9 inhibitor z-LEHD.fmk before ischemia can significantly reduce the activation of caspase-3 caused by ischemia, while the caspase-8 inhibitor z-IETD-fmk has no such effect

Method used

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  • Small peptide TAT-AVPY for treating ischemic brain damage, and application thereof
  • Small peptide TAT-AVPY for treating ischemic brain damage, and application thereof
  • Small peptide TAT-AVPY for treating ischemic brain damage, and application thereof

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Embodiment 1

[0023] In the embodiment of the present invention, a small peptide TAT-AVPY for the treatment of ischemic brain injury, wherein TAT is an 11-amino acid sequence YGRKKRRQRRR on the lentivirus, and AVPY is based on blocking the relationship between procaspase-9 and XIAP in brain ischemia It is designed to increase binding and transnitrosylation after blood and reperfusion. The full sequence of the small peptide TAT-AVPY is: H-YGRKKRRQRRR-AVPY-OH, as shown in SEQ ID NO:1.

[0024] After cerebral ischemia, endogenous procaspase-9 undergoes denitrosylation and hydrolytic activation, leading to cell apoptosis. The activity of Caspases is regulated by Inhibitors of Apoptosis (IAPs), among which X-linked Inhibitors of Apoptosis (XIAP) directly binds to procaspase-9 through its BIR domain and inhibits its activity. After cerebral ischemia, XIAP undergoes nitrosylation, thereby inhibiting its own anti-apoptotic activity.

[0025] According to the amino acid sequence of the binding site b...

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Abstract

The invention discloses a small peptide TAT-AVPY for treating ischemic brain damage, and an application thereof. The complete sequence of the small peptide TAT-AVPY is H-YGRKKRRQRRR-AVPY-OH, represented by SEQ ID NO:1. With the small peptide TAT-AVPY provided by the invention, the binding of XIAP and proaspase-9 (Casp 9) can be reduced; nitrosylation of XIAP and proaspase-9 (Casp 9) can be alleviated; and proaspase-9 activation can be alleviated. Therefore, cell apoptosis induced by cerebral ischemia can be alleviated. Also, TAT can directly bring fused small peptide into cells, such that a problem of the approach for the drug to enter cells is solved, and medication is convenient. The small peptide TAT-AVPY has no immunogenicity, and does not cause an immune response of a body. Therefore, side effects are reduced, and the effectiveness of secondary medication or more is ensured.

Description

technical field [0001] The invention relates to the field of medical technology, in particular to a small peptide TAT-AVPY for treating ischemic brain injury and its application. Background technique [0002] Stroke is one of the top three causes of death worldwide. Among them, ischemic stroke is the main type of stroke, which has the characteristics of high disability rate and high mortality rate. With the aging of the population and the increase of various risk factors, the proportion of ischemic stroke is still increasing. Ischemic stroke (stroke) includes cerebral thrombosis, lacunar infarction, and cerebral embolism, accounting for about 70% of all strokes. A large number of neurons die during a stroke, causing irreversible damage to neurons, and the neurological sequelae left after a stroke will seriously affect the quality of life of patients. However, many neuroprotective drugs clinically cannot effectively treat neuronal damage caused by stroke. Therefore, it is...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/08A61K38/10A61P9/10
CPCA61K38/00C07K7/08
Inventor 胡书群张登月燕宪亮王艳韩东桂淳蒋芳陈婕
Owner 许铁
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