CN103910781B - A kind of A beta peptide aggregation inhibitor - Google Patents

Abstract

The invention discloses an Aβ aggregation inhibitor, which is characterized in that its amino acid sequence is: amino terminal-CTIWYG-carboxyl terminal. The peptide sequence is detected by atomic force microscope scanning technology and further evaluated by cytotoxicity experiment. It has a good inhibitory effect on the aggregation of Aβ, the main toxic body that causes Alzheimer's disease, and can be tried to be developed as a drug for treating Alzheimer's disease.

Description

An Aβ aggregation inhibitor

technical field

The invention relates to an Aβ aggregation inhibitor, in particular to an anti-Alzheimer's disease toxic body Aβ inhibitor.

Background technique

At present, at least 35 million people worldwide suffer from Alzheimer's disease, and the annual death rate is rising. The total annual global cost is estimated to reach 200 billion U.S. dollars. Studies have shown that Aβ (Amyloidβ-peptide) oligomers are significant toxic substances in patients with Alzheimer's disease, so inhibiting the generation of Aβ oligomers is the most effective way to prevent Alzheimer's disease. strategy. However, there is currently no effective method for the design of Aβ inhibitors, mainly facing three serious challenges: 1. Lack of effective high-throughput screening methods: experimental screening methods need to synthesize and purify Aβ, which is undoubtedly a challenge for the screening of a large number of compounds Time-consuming, expensive and impractical. 2. Lack of high-resolution structures of Aβ oligomers: Aβ oligomers are in a metastable state, so it is difficult to obtain their structures using X-ray diffraction and NMR techniques, making rational drug design based on structures difficult to achieve. 3. Lack of understanding of Aβ self-assembly mechanism: including which part of the peptide plays a key role in the process of amyloid fibril generation; what are the pathways and intermediates related to seed and fiber generation; whether Aβ has affinity to specific receptors body; how Aβ generates the toxic body and what is the mechanism of toxicity. Therefore, designing new Aβ inhibitors has important practical significance for the diagnosis and treatment of Alzheimer's disease.

Contents of the invention

In view of this, in order to solve the above problems, the present invention provides an Aβ aggregation inhibitor whose amino acid sequence is: amino terminal-CTIWYG-carboxyl terminal, which can be developed as an anti-Alzheimer's disease therapeutic drug.

Description of drawings

In order to make the purpose, technical solutions and advantages of the present invention clearer, the present invention will be described in further detail below in conjunction with the accompanying drawings, wherein:

Figure 1 is the atomic force microscope scanning results of the newly designed peptide CTIWYG on the inhibitory effect of Aβ.

detailed description

1) Atomic force microscope scanning experiment of the peptide's inhibitory effect on Aβ;

Using a single-beam silicon cantilever detector, measured in Tapping Mode, scan at least 4 regions to ensure that the structure is properly sampled. Fig. 1 is the atomic force microscope scanning result of the inhibitory effect of the newly designed peptide CTIWYG on Aβ. It can be seen that after 2 days, CTIWYG has a significant inhibitory effect on Aβ. This peptide can be used as an Aβ aggregation inhibitor, and its sequence is: amino terminal-CTIWYG-carboxyl terminal.

Figure 1 AFM scanning results of the inhibitory effect of the newly designed peptide CTIWYG on Aβ (Tapping mode, A is the control experiment (no inhibitor), the concentration of Aβ is 1 μM, the concentration of Aβ in B is 20 μM, and the concentration of hexapeptide is 50 μM, stored for 2 days at 37°C).

e) Cytotoxicity test;

Live cells were labeled with green fluorescence by Polyanionic dyecalcein, and its activity was measured, and ethidium-1 staining was used to label dead cells with red fluorescence. Compared with the inactivation of cells caused by Aβ, after adding CTIWYG and freshly prepared Aβ to co-culture with cells, the corresponding rate of dead and alive cells was 0.412, which can significantly reduce cell apoptosis compared to the control experiment without adding peptides. When the peptide was mixed with the Aβ solution stored for 24 hours and the cells, the ratio of dead to alive cells was detected to be 0.780.

The above descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and equivalent technologies thereof, the present invention also intends to include these modifications and variations.

<110> Chongqing University

<120>An Aβ aggregation inhibitor

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<160>1

<210>1

<211>6

<212>PRT

<213> Artificial sequence

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<400>1

CysThrIlePheTyrGly

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Claims (1)

1. an A beta peptide aggregation inhibitor, is characterized in that its aminoacid sequence is: aminoterminal-CTIWYG-carboxyl terminal.