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Short peptide blocking long-term synaptic potentiation (LTP) and application thereof

A technology of long-term enhancement and short peptides, which is applied in the field of biomedicine to achieve high specificity, wide application prospects, and increased applicability and application range.

Active Publication Date: 2017-05-10
KUNMING INST OF ZOOLOGY CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] So far, no pharmacological means have been reported in the literature to selectively block the expression of LTP in synaptic plasticity without affecting NMDA receptor function and its signal transduction

Method used

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  • Short peptide blocking long-term synaptic potentiation (LTP) and application thereof
  • Short peptide blocking long-term synaptic potentiation (LTP) and application thereof
  • Short peptide blocking long-term synaptic potentiation (LTP) and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] The synthesis of embodiment 1 short peptide of the present invention

[0030] The short peptide sequence KEGYNVYGIE (KE10) or KEGYNVYGLE (KE10A) of the present invention and its control peptide KGAEVGINEA (SKE10) or modified peptides were synthesized by known and mature methods in the art, and were synthesized by GL Biochem (Shanghai) Co., Ltd. Such as figure 1 , figure 2 with image 3 As shown in the HPLC chromatogram, all synthetic short peptide products were analyzed for purity by high-pressure liquid chromatography (HPLC), and the purity was greater than 90%, which met the design requirements.

[0031] Embodiment 2 short peptide modified peptide

[0032]The invention discloses that without changing the spatial structure and stability of the short peptide, the N-terminus and the C-terminus of the short peptide are respectively modified to penetrate the cell membrane function and fluorescent labeling, so as to increase the function of the short peptide to penetrat...

Embodiment 3

[0036] Example 3 Activity of short peptides: short peptides KE10 and KE10A can block the expression of synaptic plasticity LTP, but have no effect on synaptic plasticity LTD.

[0037] (1) Experimental method

[0038] In this experiment, short peptides KEGYNVYGIE (KE10) and KEGYNVYGLE (KE10A) were selected for experiments; at the same time, a series of control experiments were performed with the control sequence short peptide KGAEVGINEA (SKE10) as a control short peptide.

[0039] Male SD rats aged 19-21 were selected, and the electrophysiological technique of isolated brain slices was used to record the synaptic plasticity in the CA1 region of the hippocampus. For the specific method, refer to the paper published by Han Huili et al. The brief description is as follows: Animals were anesthetized with ether until the muscle tension disappeared, and the rapid beheaded. After the skull is peeled off to expose the brain surface, the whole brain is taken out, trimmed into the desir...

Embodiment 4

[0048] Example 4 Activity of Short Peptide Modified Peptide: The modified peptide Tat-KE10 of short peptide KE10 can also block the expression of synaptic plasticity LTP

[0049] (1) Experimental method

[0050] In this experiment, the short peptide KEGYNVYGIE (KE10) was selected to connect with the Tat short peptide (YGRKKRRQRRR) with the ability to penetrate the cell membrane to form Tat-KE10. A short peptide, forming Tat-SKE10, was used as a control short peptide for a control experiment.

[0051] Select 18-22g male Kunming mice, and use isolated brain slice electrophysiological techniques to record synaptic plasticity in the CA1 region of the hippocampus. The preparation method of the brain slices was consistent with that of Example 3. Since the polypeptide can freely penetrate the cell membrane and enter the cell after being modified with a membrane-penetrating peptide, the administration method can be administered through circulating fluid. Under this experimental con...

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Abstract

The invention discloses a short peptide blocking long-term synaptic potentiation (LTP) and application thereof and belongs to the field of biological chemistry. A bioinformatics method is adopted to analyze human homologous sequences of different species of AMPA receptor subunits GluR2, it is found that a high conserved domain exists at the terminal C of GluR2, and the short peptide is designed on the basis and further comprises a short peptide modification peptide having cytomembrane penetrating capacity and a short peptide modification peptide marked with a fluorescent group. Amino acid sequences of the short peptide are shown as SEQ ID NO.1 and SEQ ID NO.2. The short peptide or the short peptide modification peptide can block LTP expression and has no influence on functions of LTD and NMDA receptors having synaptic plasticity. Therefore, the short peptide or the short peptide modification peptide is applied to preparation of drugs for treating or preventing diseases related to glutamic acid overexcitation diseases and pathological synaptic plasticity LTP, or establishment of experimental animal models of the diseases related to glutamic acid overexcitation diseases and the pathological synaptic plasticity LTP.

Description

technical field [0001] The invention discloses a short peptide for blocking synaptic long-term potentiation (LTP) and its application, especially the application in the field of biomedicine, which belongs to the field of biochemistry. Background technique [0002] The presynaptic membrane of nerve cells releases neurotransmitters, which act on the receptors of the postsynaptic membrane of nerve cells to form synaptic information transmission between nerve cells. The plasticity of synaptic information transmission endows the plasticity of brain function and structure, which is the fundamental basis of almost all higher brain functions. According to the neurotransmitter, synapses can be divided into excitatory synapses and inhibitory synapses. Glutamate is an excitatory neurotransmitter, and its ionotropic receptors mainly include NMDA (N-methyl-D-aspartic acid receptor, N-methyl-D-aspartic acid receptor) and AMPA receptor (α- Amino-3-hydroxy-5-methyl-4-isoxazole propionic a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06A61K38/08A61P25/00
CPCA61K38/00C07K7/06
Inventor 徐林黄京飞周启心李功华谭继伟熊贵静韩会丽
Owner KUNMING INST OF ZOOLOGY CHINESE ACAD OF SCI
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