CN103910781A - A beta aggregation inhibitor - Google Patents
A beta aggregation inhibitor Download PDFInfo
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- CN103910781A CN103910781A CN201410100093.5A CN201410100093A CN103910781A CN 103910781 A CN103910781 A CN 103910781A CN 201410100093 A CN201410100093 A CN 201410100093A CN 103910781 A CN103910781 A CN 103910781A
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- beta
- aggregation inhibitor
- ctiwyg
- beta aggregation
- peptide
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Abstract
The invention discloses an A beta aggregation inhibitor, which is characterized in that an amino acid sequence of the A beta aggregation inhibitor is amino terminal-CTIWYG-carboxyl terminal. A peptide sequence is detected through an atomic force microscope scanning technology, and is obtained through evaluation from the cytotoxicity experiments. The A beta aggregation inhibitor has good inhibition effect on aggregation of main toxicity body-A beta which can lead to alzheimer disease, and can be developed as a drug for treating alzheimer disease.
Description
Technical field
The present invention relates to a kind of toxicity body A beta inhibitor of A beta peptide aggregation inhibitor, particularly a kind of anti-Alzheimer disease.
Background technology
At present, the whole world has at least 3,500 ten thousand people to suffer from alzheimer's disease, and annual lethality rate rises.Total cost in the annual whole world is estimated to reach 2,000 hundred million dollars, research shows, A β (Amyloid β-peptide) oligomer is the remarkable toxicity body in senile dementia patient body, and the generation that therefore suppresses A beta oligomers is to stop senile dementia that the most effectively strategy occurs.But, design for A beta inhibitor without effective ways at present, the main serious challenge in the face of three aspects:: 1, lack effective high-throughput screening method: experiment screening method need to be synthesized the β with purifying A, this screening for a large amount of compounds is time-consuming beyond doubt, expensive and unrealistic.2, lack the high resolution structures of A beta oligomers: A beta oligomers is metastable state, therefore utilize X-ray diffraction and NMR technology to be difficult to obtain its structure, make to be difficult to realize based on the Rational drug design of structure.3, lack the understanding to A β self-assembly mechanism: which part that comprises peptide is formed in amyloid fiber generative process and plays keying action; Seed and fiber generate relevant path and what intermediate is; Whether A β is affine to specific acceptor; What the mechanism how A β generates toxicity body and toxicity is.Therefore, design new A beta inhibitor has important practice significance to senile dementia diagnosis and treatment.
Summary of the invention
In view of this, in order to address the above problem, the invention provides a kind of A beta peptide aggregation inhibitor, its aminoacid sequence is: aminoterminal-CTIWYG-carboxyl terminal, can attempt being developed as anti-Alzheimer disease medicine.
Brief description of the drawings
In order to make the object, technical solutions and advantages of the present invention clearer, below in conjunction with accompanying drawing, the present invention is described in further detail, wherein:
Fig. 1 is that new designed peptide CTIWYG is to the inhibiting afm scan result of A β.
Embodiment
1) peptide is to the inhibiting afm scan experiment of A β;
By single beam silicon cantilever probe, under the pattern of rapping (Tapping Mode) pattern, measure, at least scan 4 regions and correctly sample to guarantee structure.Fig. 1 be new designed peptide CTIWYG to the inhibiting afm scan result of A β, can find out, through 2 days, CTIWYG had obvious restraining effect to A β.This peptide can be used as A beta peptide aggregation inhibitor, and its sequence is: aminoterminal-CTIWYG-carboxyl terminal.
The new designed peptide CTIWYG of Fig. 1 to the inhibiting afm scan result of A β (Tapping pattern, A is control experiment (unrestraint agent), the concentration of A β is 1 μ m, in B, the concentration of A β is 20 μ M, the concentration of six peptides is 50 μ M, deposits 37 DEG C 2 days).
E) cell toxicity test;
Viable cell is carried out to green fluorescence mark with Polyanionic dye calcein, and measure its activity, ethidium-1 dyeing is carried out red fluorescence mark to dead cell.With respect to the cell inactivation being caused by A β, add after CTIWYG and freshly prepd A β and cell co-culture, corresponding death is 0.412 with becoming living cell rate, can reduce significantly apoptosis with respect to the control experiment that does not add peptide.After peptide mixes with cell with the A β solution of depositing 24 hours, obtaining after testing dead and viable cell ratio is 0.780.
The foregoing is only the preferred embodiments of the present invention, be not limited to the present invention, obviously, those skilled in the art can carry out various changes and modification and not depart from the spirit and scope of the present invention the present invention.Like this, if these amendments of the present invention and within modification belongs to the scope of the claims in the present invention and equivalent technologies thereof, the present invention is also intended to comprise these changes and modification interior.
Claims (1)
1. an A beta peptide aggregation inhibitor, is characterized in that its aminoacid sequence is: aminoterminal-CTIWYG-carboxyl terminal.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410100093.5A CN103910781B (en) | 2014-03-18 | 2014-03-18 | A kind of A beta peptide aggregation inhibitor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410100093.5A CN103910781B (en) | 2014-03-18 | 2014-03-18 | A kind of A beta peptide aggregation inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103910781A true CN103910781A (en) | 2014-07-09 |
| CN103910781B CN103910781B (en) | 2016-02-17 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201410100093.5A Expired - Fee Related CN103910781B (en) | 2014-03-18 | 2014-03-18 | A kind of A beta peptide aggregation inhibitor |
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| CN (1) | CN103910781B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108676065A (en) * | 2018-05-24 | 2018-10-19 | 华南理工大学 | The tetrapeptide of anti-aβ protein aggregation a kind of and its application and the gene for encoding the tetrapeptide |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009131975A1 (en) * | 2008-04-22 | 2009-10-29 | Schering Corporation | Phenyl-substituted 2-imino-3-methyl pyrrolo pyrimidinone compounds as bace-1 inhibitors, compositions, and their use |
| WO2010098487A1 (en) * | 2009-02-26 | 2010-09-02 | Eisai R&D Management Co., Ltd. | Nitrogen-containing fused heterocyclic compounds and their use as beta amyloid production inhibitors |
| WO2011044181A1 (en) * | 2009-10-08 | 2011-04-14 | Schering Corporation | Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| CN102180947A (en) * | 2011-02-25 | 2011-09-14 | 重庆大学 | A beta aggregation inhibitor |
| CN102218055A (en) * | 2010-08-31 | 2011-10-19 | 南京大学医学院附属鼓楼医院 | Medicament for treating Alzheimer disease(AD) |
| CN102516359A (en) * | 2011-12-08 | 2012-06-27 | 重庆大学 | Novel anti-senile dementia lead compound |
| CN102675419A (en) * | 2011-03-16 | 2012-09-19 | 上海博智生物科技有限公司 | Abeta oligopeptide polymerization inhibitor and preparation and application thereof |
-
2014
- 2014-03-18 CN CN201410100093.5A patent/CN103910781B/en not_active Expired - Fee Related
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009131975A1 (en) * | 2008-04-22 | 2009-10-29 | Schering Corporation | Phenyl-substituted 2-imino-3-methyl pyrrolo pyrimidinone compounds as bace-1 inhibitors, compositions, and their use |
| WO2010098487A1 (en) * | 2009-02-26 | 2010-09-02 | Eisai R&D Management Co., Ltd. | Nitrogen-containing fused heterocyclic compounds and their use as beta amyloid production inhibitors |
| WO2011044181A1 (en) * | 2009-10-08 | 2011-04-14 | Schering Corporation | Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| CN102218055A (en) * | 2010-08-31 | 2011-10-19 | 南京大学医学院附属鼓楼医院 | Medicament for treating Alzheimer disease(AD) |
| CN102180947A (en) * | 2011-02-25 | 2011-09-14 | 重庆大学 | A beta aggregation inhibitor |
| CN102675419A (en) * | 2011-03-16 | 2012-09-19 | 上海博智生物科技有限公司 | Abeta oligopeptide polymerization inhibitor and preparation and application thereof |
| CN102516359A (en) * | 2011-12-08 | 2012-06-27 | 重庆大学 | Novel anti-senile dementia lead compound |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108676065A (en) * | 2018-05-24 | 2018-10-19 | 华南理工大学 | The tetrapeptide of anti-aβ protein aggregation a kind of and its application and the gene for encoding the tetrapeptide |
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| Publication number | Publication date |
|---|---|
| CN103910781B (en) | 2016-02-17 |
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