CN103910782A - A beta aggregation inhibitor - Google Patents
A beta aggregation inhibitor Download PDFInfo
- Publication number
- CN103910782A CN103910782A CN201410100162.2A CN201410100162A CN103910782A CN 103910782 A CN103910782 A CN 103910782A CN 201410100162 A CN201410100162 A CN 201410100162A CN 103910782 A CN103910782 A CN 103910782A
- Authority
- CN
- China
- Prior art keywords
- beta
- aggregation inhibitor
- beta aggregation
- peptide
- present
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
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, to the invention provides a kind of its aminoacid sequence of A beta peptide aggregation inhibitor and be: aminoterminal-CTVFWG-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 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, 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 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.
The new designed peptide CTVFWG 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 CTVFWG and freshly prepd A β and cell co-culture, corresponding death is 0.508 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 0.702.
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 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-CTVFWG-carboxyl terminal.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410100162.2A CN103910782B (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 |
|---|---|---|---|
| CN201410100162.2A CN103910782B (en) | 2014-03-18 | 2014-03-18 | A kind of A beta peptide aggregation inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103910782A true CN103910782A (en) | 2014-07-09 |
| CN103910782B CN103910782B (en) | 2016-01-06 |
Family
ID=51036829
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410100162.2A Expired - Fee Related CN103910782B (en) | 2014-03-18 | 2014-03-18 | A kind of A beta peptide aggregation inhibitor |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103910782B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| WO2013004399A1 (en) * | 2011-07-07 | 2013-01-10 | Agency For Science, Technology And Research | Anti - amyloidogenic, alpha-helix breaking ultra-small peptide therapeutics |
-
2014
- 2014-03-18 CN CN201410100162.2A patent/CN103910782B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013004399A1 (en) * | 2011-07-07 | 2013-01-10 | Agency For Science, Technology And Research | Anti - amyloidogenic, alpha-helix breaking ultra-small peptide therapeutics |
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103910782B (en) | 2016-01-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Frati et al. | Diffuse axonal injury and oxidative stress: a comprehensive review | |
| Cavallari et al. | Metabolic Studies of Tumor Cells Using [1‐13C] Pyruvate Hyperpolarized by Means of PHIP‐Side Arm Hydrogenation | |
| Baek et al. | Monitoring the effects of doxorubicin on 3D-spheroid tumor cells in real-time | |
| Ahmed et al. | Molecular mechanism for the (−)-epigallocatechin gallate-induced toxic to nontoxic remodeling of Aβ oligomers | |
| Ding et al. | Furin‐controlled Fe3O4 nanoparticle aggregation and 19F signal “Turn‐On” for precise MR imaging of tumors | |
| Sgourakis et al. | Modeling an in-register, parallel “iowa” aβ fibril structure using solid-state NMR data from labeled samples with rosetta | |
| Bobylev et al. | Fullerenolates: metallated polyhydroxylated fullerenes with potent anti-amyloid activity | |
| Bousejra-ElGarah et al. | Iron (II) binding to amyloid-β, the Alzheimer’s peptide | |
| Everett et al. | Evidence of redox-active iron formation following aggregation of ferrihydrite and the Alzheimer’s disease peptide β-amyloid | |
| Liu et al. | Observation of reduced cytotoxicity of aggregated amyloidogenic peptides with chaperone-like molecules | |
| ES2381380T3 (en) | 13C-RM imaging or cell death spectroscopy | |
| CN103992379A (en) | A beta aggregation inhibitor | |
| Morita et al. | Detecting the metabolism of individual yeast mutant strain cells when aged, stressed or treated with antioxidants with diamond magnetometry | |
| Freitas-Andrade et al. | Danegaptide enhances astrocyte gap junctional coupling and reduces ischemic reperfusion brain injury in mice | |
| Sun et al. | Structural analysis of the pyroglutamate‐modified isoform of the Alzheimer's disease‐related amyloid‐β using NMR spectroscopy | |
| Zhao et al. | Design of carboxylated single-walled carbon nanotubes as highly efficient inhibitors against Aβ40 fibrillation based on the HyBER mechanism | |
| CN103910781A (en) | A beta aggregation inhibitor | |
| Kola et al. | A comparative study between lycorine and galantamine abilities to interact with AMYLOID β and reduce in vitro neurotoxicity | |
| CN103910782A (en) | A beta aggregation inhibitor | |
| CN103992380A (en) | A beta aggregation inhibitor | |
| Lupaescu et al. | Zinc binding to NAP-type neuroprotective peptides: nuclear magnetic resonance studies and molecular modeling | |
| CN102516359B (en) | Anti-senile dementia lead compound | |
| ELGAVISH | Shift-Reagent–Aided 23Na NMR Spectroscopy | |
| Cui et al. | Humanin Rescues Cultured Rat Cortical Neurons from NMDA‐Induced Toxicity Not by NMDA Receptor | |
| CN103524368B (en) | A kind of Gd coordination compound and synthetic method strengthening probe as solution paramagnetic relaxation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20160106 Termination date: 20170318 |