CN103992380B - A kind of A beta peptide aggregation inhibitor - Google Patents
A kind of A beta peptide aggregation inhibitor Download PDFInfo
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- CN103992380B CN103992380B CN201410100022.5A CN201410100022A CN103992380B CN 103992380 B CN103992380 B CN 103992380B CN 201410100022 A CN201410100022 A CN 201410100022A CN 103992380 B CN103992380 B CN 103992380B
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- aggregation inhibitor
- beta peptide
- peptide
- peptide aggregation
- beta
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Abstract
The invention discloses a kind of A beta peptide aggregation inhibitor, it is characterised in that its aminoacid sequence is: aminoterminal-VTLWYG-c-terminus.This peptide sequence, through afm scan technology for detection, obtains with cytotoxicity experiment evaluation further.The gathering of its major toxicity body-A β to causing Alzheimer has good inhibitory action, can attempt exploitation for therapeutic agent for alzheimer's disease.
Description
Technical field
The present invention relates to the toxicity body A beta inhibitor of a kind of A beta peptide aggregation inhibitor, particularly a kind of anti-Alzheimer disease.
Background technology
At present, the whole world has at least 35,000,000 people to suffer from Alzheimer, and annual fatality rate rises.Total cost estimation in the annual whole world reaches 200,000,000,000 dollars, research shows, A β (Amyloid β-peptide) oligomer is the notable toxicity body in senile dementia patient body, and the generation therefore suppressing A beta oligomers is to stop senile dementia that maximally effective strategy occurs.But, at present without effective ways for the design of A beta inhibitor, main in the face of the serious challenge of three aspects: 1, to lack effective high-throughput screening method: the synthesis of experiment screening method needs and purification A β, this is time-consuming beyond doubt, expensive and unrealistic for the screening of a large amount of compounds.2, lack the high resolution structures of A beta oligomers: A beta oligomers is metastable state, hardly result in its structure hence with X-ray diffraction and NMR technology, make to be difficult to based on the Rational drug design of structure.3, the understanding to A β self assembly mechanism is lacked: which part including peptide is formed in amyloid fiber generation process and plays pivotal role;It is what that seed generates relevant path with intermediate with fiber;Whether A β is affine to specific receptor;How A β generates what the mechanism of toxicity body and toxicity is.Therefore, senile dementia is diagnosed and treated and has important practice significance by design new A beta inhibitor.
Summary of the invention
In view of this, in order to solve the problems referred to above, the invention provides a kind of A beta peptide aggregation inhibitor, its aminoacid sequence is: aminoterminal-VTLWYG-c-terminus, can attempt exploitation for anti-Alzheimer disease medicine.
Accompanying drawing explanation
In order to make the object, technical solutions and advantages of the present invention clearly, below in conjunction with accompanying drawing, the present invention is described in further detail, wherein:
Fig. 1 is that new designed peptide VTLWYG is to the inhibiting afm scan result of A β.
Detailed description of the invention
1) peptide is to the inhibiting afm scan experiment of A β;
By single beam silicon cantilever probe, measuring under tapping-mode (TappingMode) pattern, at least 4 regions of scanning are to guarantee that structure is correctly sampled.Fig. 1 is that new designed peptide VTLWYG is to the inhibiting afm scan result of A β, it can be seen that through 2 days, A β was had obvious inhibitory action by VTLWYG.This peptide can as A beta peptide aggregation inhibitor, and its sequence is: aminoterminal-VTLWYG-c-terminus.
Fig. 1 new designed peptide VTLWYG to the inhibiting afm scan result of A β (Tapping pattern, A is control experiment (unrestraint agent), and the concentration of A β is 1 μm, in B, the concentration of A β is 20 μMs, the concentration of six peptides is 50 μMs, deposits 2 days, 37 DEG C).
E) cell toxicity test;
With Polyanionicdyecalcein, living cells carrying out green fluorescent label, and measure its activity, dead cell is carried out red fluorescence labelling by ethidium-1 dyeing.Relative to the cell inactivation caused by A β, after adding VTLWYG and freshly prepd A β and cell co-culture, corresponding death and viable cells rate are 0.602, can significantly reduce apoptosis relative to the control experiment not adding peptide.When peptide with deposit 24 little time A β solution mix with cell after, obtaining dead and living cells ratio after testing is 0.882.
The foregoing is only the preferred embodiments of the present invention, be not limited to the present invention, it is clear that the present invention can be carried out various change and modification without deviating from the spirit and scope of the present invention by those skilled in the art.So, if these amendments of the present invention and modification belong within the scope of the claims in the present invention and equivalent technologies thereof, then the present invention is also intended to comprise these change and modification.
<110>University Of Chongqing
<120>a kind of A beta peptide aggregation inhibitor
<140>
<141>
<160>1
<210>1
<211>6
<212>PRT
<213>artificial sequence
<220>
<223>
<400>1
ValThrLeuPheTyrGly
15
Claims (1)
1. an A beta peptide aggregation inhibitor, it is characterised in that its aminoacid sequence is: aminoterminal-VTLWYG-c-terminus.
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CN201410100022.5A CN103992380B (en) | 2014-03-18 | 2014-03-18 | A kind of A beta peptide aggregation inhibitor |
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CN201410100022.5A CN103992380B (en) | 2014-03-18 | 2014-03-18 | A kind of A beta peptide aggregation inhibitor |
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CN103992380A CN103992380A (en) | 2014-08-20 |
CN103992380B true CN103992380B (en) | 2016-07-06 |
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Citations (1)
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CN101863962A (en) * | 2010-05-07 | 2010-10-20 | 清华大学 | Polypeptide for inhibiting enzyme digestion of beta secretase and application thereof |
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2014
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Patent Citations (1)
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CN101863962A (en) * | 2010-05-07 | 2010-10-20 | 清华大学 | Polypeptide for inhibiting enzyme digestion of beta secretase and application thereof |
Non-Patent Citations (1)
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WP_017517243.1;none;《GenBank》;20130628 * |
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CN103992380A (en) | 2014-08-20 |
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