Polypeptide fragment and medical application thereof

A technology of polypeptide fragments and drugs, which is applied in the field of medicine, can solve problems such as limited effects, and achieve the effects of reducing release rate, improving survival rate, and reducing cell apoptosis

Active Publication Date: 2021-06-04
HEBEI ZHITONG BIOLOGICAL PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Currently commonly used drugs are cholinesterase inhibitors, etc., but they are all symptomatic treatments with limited effects. 25-35 Drugs that cause memory dysfunction pose challenges

Method used

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  • Polypeptide fragment and medical application thereof
  • Polypeptide fragment and medical application thereof
  • Polypeptide fragment and medical application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] The artificial synthesis method of embodiment 1 peptide segment NYEPPTVVPGGDL

[0018] The peptide chain was synthesized by Fmoc / PyBOP method. The removal of Fmoc protecting group adopts the DMF solution of 30% hexahydropyridine; The cutting off of peptide chain from the resin adopts peptide cutting reagent (trifluoroacetic acid / crystalline phenol / water / thioanisole / ethanedithiol / methyl ethyl sulfide Ether = 81.5 / 5 / 5 / 5 / 2.5 / 1).

[0019] Step 1: Resin treatment before peptide grafting

[0020] i) Weigh 10 g of BOC-Leu-Merrifield resin (purchased from Merck) into a sand core filter reactor.

[0021] ii) add dichloromethane to soak and wash 6 times, 15 ml each time, and filter to remove the washed dichloromethane.

[0022] iii) Add 15 ml of 10% TFA (dichloromethane as solvent) and react at room temperature for 2 hours to remove the BOC protecting group at the N-terminal of the amino acid on the resin.

[0023] iv) add dichloromethane to soak and wash 3 times, 15 millilit...

Embodiment 2

[0053] Example 2 Peptide NYEPPTVVPGGDL in the treatment of Aβ 25-35 Research on nerve cell damage

[0054] Step 1: Experimental grouping (adrenal pheochromoma cells PC12 cells, donated by Mr. Xu Ming, China Pharmaceutical University, n=5)

[0055] i) Control group: spot 96-well plate with 8*10^3 / well, adhere to the wall for 12 hours, change to serum-free medium and culture for 12 hours, then change to fresh serum-free medium and continue to culture for 48 hours.

[0056] ii) Modeling group: spot 96-well plates with 8*10^3 / well, adhere to the wall for 12 hours, replace with serum-free medium and culture for 12 hours, and then replace with freshly prepared Aβ in serum-free medium 25-35 (20μM) to continue to culture for 48h.

[0057] iii) Peptide 10 μg / ml pre-administered group: spot 96-well plates with 8*10^3 / well, adhere to the wall for 12 hours, replace with freshly prepared peptide solution (10 μg / ml) in serum-free medium and incubate for 12 hours, Replace with freshly pre...

Embodiment 3

[0085] Example 3 Peptide NYEPPTVVPGGDL in the treatment of Aβ 25-35 Study on memory dysfunction

[0086] Step 1: Experimental grouping (6-week-old C57 male mice, purchased from the Comparative Medicine Center of Yangzhou University, n=6)

[0087] i) Sham operation group: 4 days pre-administration of equal volume of normal saline (0.1ml / 20g). After the sham operation, an equal volume of normal saline (0.1ml / 20g) was injected intraperitoneally.

[0088] ii) Modeling group: 4 days pre-administration of equal volume of normal saline (0.1mL / 20g). After modeling, an equal volume of saline (0.1 mL / 20 g) was injected intraperitoneally.

[0089] iii) Peptide 10 mg / kg pre-administration group: peptide NYEPPTVVPGGDL (10 mg / kg*day) was pre-administered for 4 days. After modeling, an equal volume of peptide NYEPPTVVPGGGSH (0.1 mL / 20 g) was injected intraperitoneally.

[0090] iv) Peptide 1 mg / kg pre-administration group: 4-day pre-administration of peptide NYEPPTVVPGGDL (1 mg / kg*day)....

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PUM

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Abstract

The invention discloses an artificially synthesized polypeptide fragment NYEPPTVVPGGDL, also discloses an application of the artificially synthesized polypeptide fragment NYEPPTVVPGGDL in preparation of a medicine for preventing and treating memory dysfunction caused by beta amyloid peptide 25-35 (A beta 25-35), and belongs to the field of pharmacy. By establishing a nerve injury cell model for giving A beta 25-35 stimulation to rat adrenal chromaffin tumor (PC12) cells, it is found that the peptide fragment can significantly improve the survival rate of the cells and the like; and in a mouse memory dysfunction model in which A beta 25-35 is injected into unilateral hippocampus, the peptide fragment is found to be capable of remarkably improving the memory dysfunction of mice. Therefore, the peptide fragment can be used for preparing medicines for preventing and treating nerve injury and memory dysfunction caused by beta amyloid peptide 25-35 (A beta 25-35), comprising medicines for preventing and treating Alzheimer's disease.

Description

technical field [0001] The invention belongs to medical technology, and in particular relates to a polypeptide fragment and its medical application, especially its application in the preparation of medicines for preventing and treating memory dysfunction. Background technique [0002] Alzheimer's disease is a progressive neurodegenerative disease, and its incidence is increasing year by year, often manifested as memory dysfunction and cognitive deficits. β-amyloid peptide 25-35 (Aβ 25-35 ) is the biologically active region of the Aβ protein, which is often used to replicate the pathological damage model of Alzheimer's disease. This fragment can disrupt cell function, lead to cell death, induce neurodegeneration in vitro and in vivo, and cause memory dysfunction and cognitive deficits. [0003] Currently commonly used drugs are cholinesterase inhibitors, etc., but they are all symptomatic treatments with limited effects. 25-35 Drugs that cause memory dysfunction pose a chal...

Claims

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Application Information

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IPC IPC(8): C07K7/08A61K38/10A61P25/28
CPCC07K7/08A61P25/28A61K38/00
Inventor 梁艳王广基郭慧敏
Owner HEBEI ZHITONG BIOLOGICAL PHARMA
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