A beta aggregation inhibitor

A technology of inhibitors and amino acids, applied in neurological diseases, drug combinations, peptides, etc., can solve problems such as lack of understanding, cost, and lack of high-throughput screening methods

Inactive Publication Date: 2011-09-14
CHONGQING UNIV
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Problems solved by technology

However, there is currently no effective method for the design of AD 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

Method used

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Embodiment Construction

[0012] The following is a detailed description of the design and identification of Aβ inhibitors used in the pathogenesis of Alzheimer's disease using the method of the present invention as an example, including the following steps:

[0013] a) Quantitative structure-activity relationship modeling of peptides;

[0014] a1) Peptide structure characterization: 120 peptide samples were selected from the literature (Matsubara et al., Nat Methods, 2010, 7(3):237), including 49 aggregateable peptide samples and 71 non-aggregate peptide samples. Each peptide contains 6 amino acid residues. In order to reasonably characterize the structural characteristics of these peptides, 335 property parameters of 20 natural amino acids were selected. These variables characterize the following properties of amino acids: α-helix and turn-inclination properties; β-inclination properties ; physical and chemical properties; compositional characteristics and other characteristics. The selected variabl...

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Abstract

The invention discloses an A beta aggregation inhibitor. The aggregation inhibitor is characterized in that: the amino acid sequence of the aggregation inhibitor is amino terminal-IYVLIY-carboxyl terminal. The peptide sequence is designed based on a quantitative structure function relational model of peptide and is obtained through technical detection of microscope scan. The aggregation inhibitor has a good effect of inhibiting the aggregation of the toxic body, namely A beta capable of causing Alzheimer's disease and can be further developed into a medicament for treating the Alzheimer's disease.

Description

technical field [0001] The invention relates to an Aβ aggregation inhibitor, in particular to an anti-Alzheimer's toxicant Aβ inhibitor. Background technique [0002] Alzheimer's disease (AD) is the most common dementia in the elderly. At present, at least 35 million people worldwide suffer from this disease, and the annual fatality rate is rising. The total annual global cost is estimated to reach 200 billion US dollars. Studies have shown that Aβ (Amyloid β-peptide) oligomers are significant toxicants in AD patients, so inhibiting the generation of Aβ oligomers is the most effective strategy to prevent AD. However, there is currently no effective method for the design of AD 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. ...

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Application Information

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IPC IPC(8): C07K7/06A61P25/28
Inventor 梁桂兆郑洁刘永红马秀岩苗霞闫宁吕凤林杨力
Owner CHONGQING UNIV
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