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Small molecule polypeptide and application thereof in preparation of medicine for preventing and treating Parkinson's disease

A technology of small molecule peptides and drugs, applied in the field of biomedicine, can solve problems such as unclear specific mechanisms, achieve the effects of improving exercise capacity, reducing death and movement disorders, and reducing the loss of dopaminergic neurons

Active Publication Date: 2021-08-10
GUILIN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Many domestic and foreign scholars and our laboratory have found that knocking out or inhibiting SIRT2 can reduce the loss of dopaminergic neurons and motor dysfunction during the onset of Parkinson's disease (PD), and has a protective effect on PD, but Its exact mechanism is unclear
[0003] At present, there is no relevant research on the use of SIRT2-related small molecule peptides for the preparation of drugs for the prevention and treatment of Parkinson's

Method used

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  • Small molecule polypeptide and application thereof in preparation of medicine for preventing and treating Parkinson's disease
  • Small molecule polypeptide and application thereof in preparation of medicine for preventing and treating Parkinson's disease
  • Small molecule polypeptide and application thereof in preparation of medicine for preventing and treating Parkinson's disease

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] Embodiment 1 design polypeptide:

[0018] Containing SIRT2 protein Ser331 site and Ser335 site, the sequence is TSASPKKSPPPA twelve amino acid polypeptides (SIRT2 328-339 ), and combined myristic acid (Myristic acid, MYR) at the N-terminus of the short peptide.

[0019] The control peptide is SIRT2 328-339 The scrambled peptide (Scramble) of the peptide has a sequence of KTAPSAPKPPSS, and the N-terminus of the short peptide is also bound to myristic acid (MYR).

[0020] Entrusted to Kangwei Biotechnology Co., Ltd. to synthesize, the purity of the peptide can reach more than 95%.

Embodiment 2

[0022] Select SD rats that are 16-18 days pregnant, and take E16-18 rat embryos under aseptic conditions and place them in pre-cooled D-hanks solution. Forceps and ophthalmic scissors were used to peel off the mouse’s scalp to expose the skull. The skull was peeled off with sharp forceps along the sagittal suture of the skull and the spinal cord, and the cerebral cortex was exposed and divided into two with sharp forceps. The cerebral cortex was separated under a dissecting microscope, and the meninges and blood vessels were peeled off. , hippocampus, and midbrain were placed in another clean glass dish filled with pre-cooled D-Hanks solution, and then the cortex was digested in a 37°C incubator with 0.125% trypsin. After 2 minutes, the digestion situation was observed and further confirmed. time. Then the tissue was aspirated with a pipette tip and transferred to a centrifuge tube containing serum to terminate the trypsin digestion. After blowing with a 5ml pipette for 20 ti...

Embodiment 3

[0024] Take 60 healthy adult C57BL / 6 male mice of about 25g, and randomly divide them into four groups. One group of mice is injected with normal saline, and the other three groups of mice are intraperitoneally injected with 30mg / ml of 1-Methyl-4-phenyl-1 once a day , 2,3,6-tetra-hydropyridine hydrochloride (MPTP) was used for modeling and injected continuously for 5 days. At the same time as modeling, a group of MPTP groups were injected with MYR-Scramble peptide, and a group of MPTP groups were injected with MYR-SIRT2 328-339 Peptide, 10 consecutive days, once a day, 2mg / kg. One day after modeling, the mice were sacrificed, the whole brain was fixed and dehydrated, and the substantia nigra brain slices were cut, and the number of dopamine neurons in the substantia nigra of the mice was detected by immunofluorescence. The experimental process is as follows figure 2 As shown, the experimental results show that intraperitoneal injection of MYR-SIRT2 328-339 Peptides can redu...

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Abstract

The invention provides a small molecule polypeptide and application thereof in preparation of a medicine for preventing and treating Parkinson's disease, and relates to the technical field of biological medicine. The small molecule polypeptide is obtained by connecting an end-capping group and a short peptide, and the sequence of the short peptide is as shown in SEQ ID NO. 1. According to the small-molecule polypeptide, the problem that in the prior art, no SIRT2-related small-molecule polypeptide is used for preparing the medicine for preventing and treating the Parkinson's disease is solved, the small-molecule polypeptide MYR-SIRT2328-339 can be competitively combined with CDK5, the phosphorylation of the CDK5 on the Ser331 site and the Ser335 site of endogenous SIRT2 protein can be inhibited, and the death and dyskinesia of dopaminergic neurons during PD can be relieved.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a small molecule polypeptide and its application in the preparation of drugs for preventing and treating Parkinson's disease. Background technique [0002] Parkinson's disease (PD) is the neurodegenerative disease with the second highest incidence after Alzheimer's disease (AD). The rate increases with age, seriously affecting the health and quality of life of middle-aged and elderly people. The main pathological features of PD are the loss of midbrain dopaminergic neurons and the formation of Lewy bodies (Lewy bodies), which are proteins containing α-synuclein (α-synuclein) and ubiquitin (ubiquitin, Ub) inclusion body. Once clinical motor symptoms appear on the onset of PD, 50-60% of the dopaminergic neurons in the substantia nigra have degenerated and died, and the dopamine in the striatum has decreased by 70-80%. Age, genetics, environment, mitochondrial dysfunction, ox...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/08C07K1/107A61K38/10A61P25/16
CPCC07K7/08A61P25/16A61K38/00
Inventor 闫建国周亚莉谭洁邵晓云方方苏燕徐兴凤李茂
Owner GUILIN MEDICAL UNIVERSITY
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