Oligopeptide and application thereof

A short peptide and sequence technology, applied in the field of short peptides and their applications, can solve problems such as difficult clinical transformation

Active Publication Date: 2020-01-10
ACADEMY OF MILITARY MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Previous studies have shown that up-regulating the expression of glutamate transporter GLT-1 can reduce ischemic brain injury, but slowly regulating the expression of glutamate transporter is not enough to produce neuroprotection in the early stage of cerebral ischemia
[0003] Although the regulation of the activity of the glutamate transporter GLT-1 has shown certain prospects in the treatment of ischemic stroke, there is currently no drug that can rapidly regulate the activity of the glutamate transporter GLT-1 in ischemic stroke. drug
It is now known that lactam antibiotics can up-regulate the expression of glutamate transporters within a week, but this chronic regulation is difficult to achieve clinical transformation in the treatment of ischemic stroke, because the time window for clinical treatment of ischemic stroke is very short. short, usually only a few hours

Method used

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  • Oligopeptide and application thereof
  • Oligopeptide and application thereof
  • Oligopeptide and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1 The effect of His-2A-TAT on the activity of glutamate transporter GLT-1 caused by SHH signaling pathway

[0031] Prepare short peptides His-2A-TAT and His-SC-TAT by biological or chemical methods, the amino acid sequence of which is:

[0032] His-2A-TAT:HHHHHHLAANGKSADCSVEEEPWKREKYGRKKRRQRRR;

[0033] His-SC-TAT:HHHHHHASSGAKWKEVPECDLRKANEEYGRKKRRQRRR.

[0034] structured as figure 1 As shown, His-SC-TAT was used as the control peptide of His-2A-TAT to verify the function of His-2A-TAT. The SC sequence is a random scrambled arrangement of the 2A sequence.

[0035] First, dissolve the chemically synthesized His-2A-TAT and His-SC-TAT powders with physiological saline to a concentration of 1 mM, and add His-2A-TAT or His-SC in proportion to rat astrocytes cultured in vitro -TAT, the total concentration is 0.5 μM and 1 μM. After 4 hours, the cells are lysed with cell lysate, heated at 100 degrees Celsius for 10 minutes to denature the protein, and the denatured...

Embodiment 2

[0039] Example 2 His-2A-TAT inhibits the reduction of GLT-1 protein on the cell membrane during cerebral ischemia

[0040]The results of Example 1 confirmed that the SHH signaling pathway can rapidly regulate GLT-1 activity in cells cultured in vitro. Whether there is activation of the SHH signaling pathway in the process of ischemia in the body, for this reason, a mouse unilateral cerebral ischemia model is constructed by inserting a thread into the right carotid artery of the mouse and tethering it to the middle cerebral artery. At different time points after ischemia, take out the hippocampal tissue of the ischemic side and the ischemic side of the mouse, and infiltrate the tissue in artificial cerebrospinal fluid for 30 minutes. If the SHH protein is secreted outside the cells, it will dissolve under such conditions. After that, the artificial cerebrospinal fluid was used for ELISA (enzyme-linked immunosorbent assay) experiment, and the results were as follows: Figure 5 ...

Embodiment 3

[0043] Example 3 Evaluation of the efficacy of His-2A-TAT in the mouse model of cerebral ischemia

[0044] The experimental process is as follows Figure 7 As shown, the C57 mice purchased from Speifu, with a body weight of about 25g, were randomly divided into 10 mice in the control group (His-SC-TAT), 9 mice in the treatment group (His-2A-TAT), and 1 hour before the experiment Inject His-SC-TAT or His-2A-TAT into the tail vein according to body weight (10 mg / kg), and perform unilateral cerebral ischemia modeling as described above. Two hours later, pull out the thread tie inserted into the middle cerebral artery, and restore the brain Blood flow in the middle artery was achieved to achieve reperfusion. One day later, the brain was taken out, sliced, and soaked in TTC staining solution (a commonly used reagent for detecting the activity state of brain cells) until red color appeared. Remove TTC, add PFA, fix at 4°C, and store.

[0045] The result is as Figure 8 As shown, ...

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Abstract

The invention discloses oligopeptide and application thereof, and belongs to the field of biomedicine. The amino acid sequence of the oligopeptide is as shown in the sequence listing SEQ ID NO.1 or anamino acid sequence with the same function formed by replacing, deleting or adding one or several amino acids to the sequence. An SHH signaling pathway can rapidly regulate and control the activity of glutamate transporter GLT-1 in ischemic stroke, that is, by reducing the amount of glutamate transporter GLT-1 protein on a cell membrane, the activity of the glutamate transporter GLT-1 is reduced.His-2A-TAT can effectively prevent the reduction of the activity of the glutamate transporter GLT-1 caused by SHH, and thus a neuroprotective role in the ischemic stroke is played.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a short peptide and its application. Background technique [0002] Stroke has become the number one killer of Chinese people's health. But so far, the only drug used to treat ischemic stroke is the thrombolytic drug t-PA, but t-PA has the potential to cause cerebral hemorrhage. The strongest factor of early damage in ischemic stroke is the excitotoxicity of glutamate, but no clinical trials of drugs targeting glutamate receptors have been successful. In addition to glutamate receptors, glutamate transporters, especially the glutamate transporter named GLT-1 expressed in astrocytes, play the most important role in the process of scavenging glutamate. Previous studies have shown that up-regulating the expression of glutamate transporter GLT-1 can reduce ischemic brain injury, but slowly regulating the expression of glutamate transporter is not enough to produce neuroprotect...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00A61K38/16A61K47/64A61P9/10
CPCA61K38/00A61P9/10C07K14/001C07K2319/10C07K2319/21
Inventor 王宇青陆珊珊王以政
Owner ACADEMY OF MILITARY MEDICAL SCI
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