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Polypeptide capable of inhibiting excitable and toxic damages and use thereof

An excitatory and peptide technology, applied in the fields of application, peptide source, animal/human peptide, etc., can solve the problems of motor function damage, blocking excitatory synaptic transmission function, toxic and side effects, etc.

Inactive Publication Date: 2012-03-21
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the results of clinical experiments are disappointing. Since almost all neurons express NMDA receptors, antagonists inevitably block the normal excitatory synaptic transmission function of NMDA receptors, resulting in obvious toxic side effects, such as hallucinations and memory. Psychiatric symptoms such as disorders and impairment of motor function

Method used

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  • Polypeptide capable of inhibiting excitable and toxic damages and use thereof
  • Polypeptide capable of inhibiting excitable and toxic damages and use thereof
  • Polypeptide capable of inhibiting excitable and toxic damages and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028]Example 1, Identification of DREAM protein and NR1 subunit binding site

[0029] The full length of DREAM protein is 256 amino acids, and there is an EF hand domain in each of its 102-113, 139-150, 175-186 and 223-234 amino acids. According to this, the DREAM protein is segmented, the N-terminus is defined as 1-100 positions, the C-terminus is defined as 101-256 positions, contains 4 complete EF hand domains, and the N-terminus is further divided into 1-50 positions and 51-100 positions bit two paragraphs.

[0030] The amino acid sequence of the DREAM protein is shown in SEQ ID NO.1.

[0031] The following peptides were used in Experiment 1: DREAM 1-50 (1-50th amino acid peptide from the N-terminal of the DREAM protein shown in SEQ ID NO.1), DREAM 51-100 (the N-terminus of the DREAM protein shown in SEQ ID NO.1 51-100th amino acid peptide from the end), DREAM 101-256 (the 101-256th amino acid peptide from the N-terminal of DREAM protein shown in SEQ ID NO.1), DREAMΔ1-5...

Embodiment 2

[0070] Example 2, Application of TAT-21-40 in inhibiting excitotoxic injury

[0071] TAT (transcriptional activator protein) penetrating peptide is one of the transmembrane delivery carriers, which can introduce covalently linked polypeptides, proteins, DNA and other molecules into cells across the membrane, and even pass through the blood-brain barrier. Without damage, it has been widely used in the fields of cell biology, gene therapy and pharmacy. According to the main site where the N-terminal of DREAM binds to the NR1 subunit, that is, amino acids 21-40 at the N-terminus, a fusion peptide with membrane-penetrating ability——TAT-21-40 was constructed. The amino acid sequence of the target sequence was scrambled, and scramble-TAT was constructed as a control.

[0072] The amino acid sequence of TAT-21-40 is shown in SEQ ID NO.4, which consists of the TAT transmembrane sequence (RKKRRQRRR) and amino acids 21-40 from the N-terminus of DREAM. TAT-21-40 was synthesized by Jill...

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Abstract

The invention discloses a polypeptide inhibiting excitable and toxic damages and use thereof. The polypeptide has an amino acid sequence represented by SEQ ID NO.4. Experiments show that the polypeptide of the invention can relieve cell damages caused by NMDA before the pretreatment of an NMDA damage, protect the cell when added into the cell after the treatment of the NMDA, and prevent and cure the excitable and toxic damages induced by an NMDA receptor. Therefore, the polypeptide has wide application in the inhibition of the excitable and toxic damages.

Description

technical field [0001] The present invention relates to a polypeptide for inhibiting excitotoxic injury and its application. Background technique [0002] The concept of excitotoxicity was first proposed by Olney et al. in the 1970s. It is a process of neuron death caused by the excessive and continuous activation of glutamate receptors, the central excitatory neurotransmitter. Excessive activation of glutamate receptors further amplifies the biological effects caused by normal physiological stimuli, causing postsynaptic neurons to overexcite and eventually die. Factors such as increased release of transmitters from presynaptic neurons, decreased reuptake of transmitters by glial cells, and reverse transport of glutamate transporters can all lead to increased extracellular glutamate concentrations. In addition, increased sensitivity of glutamate receptors is also one of the factors that produce excitotoxic injury. [0003] At present, it is believed that acute brain injuri...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/47C12N15/12C12N15/63C12N1/00C12N5/10A61K38/17A61K48/00A61P9/10A61P25/00A61P25/08A61P25/16A61P25/28A61P25/14
Inventor 王韵张瑛苏萍朱彦兵韩涛
Owner PEKING UNIV
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