CN103910782B - A kind of A beta peptide aggregation inhibitor - Google Patents
A kind of A beta peptide aggregation inhibitor Download PDFInfo
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- CN103910782B CN103910782B CN201410100162.2A CN201410100162A CN103910782B CN 103910782 B CN103910782 B CN 103910782B CN 201410100162 A CN201410100162 A CN 201410100162A CN 103910782 B CN103910782 B CN 103910782B
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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 characterized in that its aminoacid sequence is: aminoterminal-CTVFWG-carboxyl terminal.This peptide sequence, through afm scan technology for detection, obtains with cytotoxicity experiment evaluation further.It has good restraining effect to the gathering of the major toxicity body-A β causing alzheimer's disease, can attempt being developed as therapeutic agent for alzheimer's 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 estimation in the annual whole world reaches 2,000 hundred million dollars, research shows, A β (Amyloid β-peptide) oligomer is the remarkable toxicity body in senile dementia patient body, therefore suppresses the generation of A beta oligomers to be stop senile dementia that the most effective strategy occurs.But, current without effective ways be used for A beta inhibitor design, the main serious challenge in the face of three aspects: 1, lack effective high-throughput screening method: the synthesis of experiment screening method needs and purifying A β, this screening for large quantization compound 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 the Rational drug design of structure based be difficult to realize.3, the understanding to A β self-assembly mechanism is lacked: which part comprising peptide is formed in amyloid fiber generative process plays keying action; Seed generates relevant path with fiber 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, to senile dementia Diagnosis and Treat, there is important practice significance.
Summary of the invention
In view of this, in order to solve the problem, the invention provides a kind of its aminoacid sequence of A beta peptide aggregation inhibitor is: aminoterminal-CTVFWG-carboxyl terminal can be attempted being developed as 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 CTVFWG 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, measure under tapping-mode (TappingMode) pattern, at least scan 4 regions to guarantee that structure is correctly sampled.Fig. 1 be new designed peptide CTVFWG to the inhibiting afm scan result of A β, can find out, through 2 days,
CTVFWG has obvious restraining effect to A β.This peptide can be used as A beta peptide aggregation inhibitor, and its sequence is: aminoterminal-CTVFWG-carboxyl terminal.
Fig. 1 new designed peptide CTVFWG 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;
Carry out green fluorescent label with Polyanionicdyecalcein to viable cell, and measure its activity, ethidium-1 dyeing carries out red fluorescence mark to dead cell.Relative to the cell inactivation caused by A β, after adding CTVFWG and freshly prepd A β and cell co-culture, corresponding death and viable cells rate are 0.508, can reduce apoptosis significantly relative to the control experiment not adding peptide.After peptide mixes with cell with the A β solution deposited 24 hours, obtaining dead and viable cell ratio is after testing 0.702.
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 change and modification to the present invention and not depart from the spirit and scope of the present invention.Like this, 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 beta peptide aggregation inhibitor
<140>
<141>
<160>1
<210>1
<211>6
<212>PRT
<213> artificial sequence
<220>
<223>
<400>1
CysThrValPheTrpGly
15
Claims (1)
1. an A beta peptide aggregation inhibitor, is characterized in that its aminoacid sequence is: aminoterminal-CTVFWG-carboxyl terminal.
Priority Applications (1)
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CN201410100162.2A CN103910782B (en) | 2014-03-18 | 2014-03-18 | A kind of A beta peptide aggregation inhibitor |
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CN201410100162.2A CN103910782B (en) | 2014-03-18 | 2014-03-18 | A kind of A beta peptide aggregation inhibitor |
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CN103910782A CN103910782A (en) | 2014-07-09 |
CN103910782B true CN103910782B (en) | 2016-01-06 |
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102492022A (en) * | 2011-12-08 | 2012-06-13 | 重庆大学 | Novel anti-senile dementia lead compound |
CN102516359A (en) * | 2011-12-08 | 2012-06-27 | 重庆大学 | Novel anti-senile dementia lead compound |
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SG187271A1 (en) * | 2011-07-07 | 2013-02-28 | Agency Science Tech & Res | Anti-amyloidogenic, alpha-helix breaking ultra-small peptide therapeutic |
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2014
- 2014-03-18 CN CN201410100162.2A patent/CN103910782B/en not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102492022A (en) * | 2011-12-08 | 2012-06-13 | 重庆大学 | Novel anti-senile dementia lead compound |
CN102516359A (en) * | 2011-12-08 | 2012-06-27 | 重庆大学 | Novel anti-senile dementia lead compound |
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CN103910782A (en) | 2014-07-09 |
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Granted publication date: 20160106 Termination date: 20170318 |