Fusion polypeptide and application of fusion polypeptide in preparing medicine for anti-depression and neurodegenerative disease

A fusion peptide, antidepressant technology, applied in nervous system diseases, hybrid peptides, drug combinations, etc., can solve the problems of limitation, short half-life, low oral utilization rate, etc., to achieve safe use, good stability, good transmembrane The effect of efficiency

Active Publication Date: 2019-09-20
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, as we all know, due to its own characteristics, peptide drugs have many shortcomings, such as low oral utilization, high enzymolysis and extremely short half-life, etc., which make them suffer from many restrictions in drug development.

Method used

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  • Fusion polypeptide and application of fusion polypeptide in preparing medicine for anti-depression and neurodegenerative disease
  • Fusion polypeptide and application of fusion polypeptide in preparing medicine for anti-depression and neurodegenerative disease
  • Fusion polypeptide and application of fusion polypeptide in preparing medicine for anti-depression and neurodegenerative disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] In this example, in the previous experimental design, the inventor screened four domains (eIF4A-Q, eIF4A-I, eIF4A-Ia, eIF4A-VI) that closely bind eIF4A and PDCD4 by consulting the literature, and their amino acid sequences are shown in the table 1. Through the method of molecular cloning, the inventor constructed a fusion protein containing the domain of interest ( figure 1 a figure 1 b). Co-immunoprecipitation ( figure 1 c) The results showed that the IB: HA band in the eIF4A-VI group was significantly lower than that of other domains and was almost colorless, proving that there was almost no interaction between eIF4A and PDCD4 in the eIF4A-VI interference group, and eIF4A-VI had good interference efficiency. At the same time, Western blot experiments ( figure 1 d) It was verified that eIF4A-VI can induce the expression of IIc-BDNF, and the induction effect is also significantly higher than that of other domain polypeptides. eIF4A-VI can also meet the functions of ...

Embodiment 2

[0070] Combined with the research results of Example 1, eIF4A-VI was selected for corresponding modification in this example, and the 9R transmembrane sequence was added to the N segment to synthesize the polypeptide 9R-eIF4A-VI. like figure 2 As shown in a, the N segment of the fusion polypeptide is the 9R transmembrane sequence, and the C segment is the eIF4A-VI domain obtained by screening. The 9R transmembrane sequence and 9R-eIF4A-VI sequence are shown in Table 2 below:

[0071] Table 2 Amino acid sequences of 9R and 9R-eIF4A-VI

[0072]

[0073] In order to detect the effect of the fusion polypeptide interfering with the combination of PDCD4 and eIF4A, the inventors designed 9R-mueIF4A-VI as a control peptide for testing, and the 9R-mueIF4A-VI randomly mutated an amino acid at one site compared with 9R-eIF4A-VI. ( figure 2 b / 2c / 2d) It was confirmed by immunoblotting that 9R-eIF4A-VI can promote the expression of IIc-BDNF, and the promoting effect is concentration...

Embodiment 3

[0080] Example 2 has confirmed that the 9R-eIF4A-VI has a good transmembrane effect and stability in the HEK-293 cell model. This example further studies the effect of the polypeptide on neuron cells.

[0081] like image 3 As shown in a, the inventors also verified the transmembrane efficiency and stability of 9R-eIF4A-VI in primary neuron cells. like image 3 b, In primary neurons, fluorescence observation shows that 9R-eIF4A-VI and PDCD4 have obvious co-localization, which further illustrates the specific interference of the polypeptide sequence on PDCD4. image 3 C shows that 9R-eIF4A-VI can promote the expression of BDNF in primary neurons. ( image 3 d) The expression of BDNF in the culture supernatant of primary neurons was detected by ELISA, and the inventor designed to increase the expression of BDNF by interfering with the combination of PDCD4 and EIF4A, thereby strengthening the intersynaptic signal transmission and alleviating depression symptoms. .

[0082] A...

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Abstract

The invention belongs to the technical field of biology, and specifically relates to a 9R-eIF4A-VI fusion polypeptide and an application of fusion polypeptide in preparing a medicine for anti-depression. The studies confirm that PDCD4 can bind to a eukaryotic translation initiation factor (eIF4A) to inhibit the expression of a brain-derived neurotrophic factor (BDNF), impedes the repair and synaptic transmission of damaged neurons, and aggravates the symptoms of the depressed patients. The application screens a number of domains in which PDCD4 binds to eIF4A, by fusion of a transmembrane sequence and a domain on eIF4A, the fusion polypeptide having the interference effect is obtained, the experiments verify that the fusion polypeptide can effectively interfere with the binding of PDCD4 and eIF4A, has good transmembrane efficiency and stability, and can be applied to the preparation of antidepressant drugs, which has great significance.

Description

technical field [0001] The disclosure belongs to the field of biotechnology, and specifically relates to a polypeptide that interferes with the combination of PDCD4 and eIF4A and the application of the fusion polypeptide 9R-eIF4A-VI as an antidepressant and an antineurodegenerative disease drug. Background technique [0002] The information disclosed in this Background section is only intended to increase the understanding of the general background of the disclosure, and is not necessarily to be taken as an acknowledgment or any form of suggestion that the information constitutes prior art that is already known to those skilled in the art. [0003] Depression is a kind of mental disorder with depressed mood as the main symptom. Severe patients even commit suicide, which seriously threatens human health. A large number of clinical research evidences show that synaptic plasticity caused by excessive activation of microglia is the pathological basis of depression. Brain-derive...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00A61K38/17A61K47/64A61P25/24
CPCA61K38/00A61P25/24C07K14/4705C07K2319/03
Inventor 张利宁贾玉峰李媛王群朱法良郭春李艳
Owner SHANDONG UNIV
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