CN106706930A - Kit for detecting Parkinson's disease - Google Patents
Kit for detecting Parkinson's disease Download PDFInfo
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- CN106706930A CN106706930A CN201710113949.6A CN201710113949A CN106706930A CN 106706930 A CN106706930 A CN 106706930A CN 201710113949 A CN201710113949 A CN 201710113949A CN 106706930 A CN106706930 A CN 106706930A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/577—Immunoassay; Biospecific binding assay; Materials therefor involving monoclonal antibodies binding reaction mechanisms characterised by the use of monoclonal antibodies; monoclonal antibodies per se are classified with their corresponding antigens
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/475—Assays involving growth factors
- G01N2333/515—Angiogenesic factors; Angiogenin
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
- G01N2800/2835—Movement disorders, e.g. Parkinson, Huntington, Tourette
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Abstract
The invention relates to a kit for detecting Parkinson's disease. The kit comprises an antibody capable of being used for specially detecting the Parkinson's disease, wherein the antibody has a good combination constant. Compared with a kit in the prior art, the kit provided by the invention has higher detection accuracy.
Description
Technical field
The present invention relates to detection field, and in particular to a kind of kit for parkinsonism detection.
Background technology
Parkinson's (PD) also known as shaking plasy, are one of most common nerve degenerative diseases.Epidemiology shows, suffers from
Sick rate is 15~3,28/,100,000 populations, 65 years old crowd about 1% of ＞；The incidence of disease is 10~21/,100,000 populations/year.The PD causes of disease and hair
Interpretation of the cause, onset and process of an illness system is not yet clear and definite, may be relevant with social factor, drug factors, patients factors etc..PD pathological changes are：Substantia nigra of midbrain is caused
Compact part, Neurons of Locus Coeruleus depigmentation, black substance pigment is thin out and Lewy body occurs.PD nerve biochemical change be：Substantia nigra of midbrain
Compact part, Neurons of Locus Coeruleus depigmentation cause dopamine (DA) at above-mentioned position and its nerve endings to reduce, and (DA is produced when reducing >=70%
Raw PD clinical manifestations), and acetylcholine (ACH) effect in nigrostriatum system with DA function antagonisms is relative hyperfunction, DA and
ACH dysequilibriums.
So far, the cause of disease of pd is still unclear.Current research trend in age ageing, genetic predisposition and environment
The composite factors such as the contact of toxin are relevant.
1) age ageing：
2) environmental factor：Epidemiology survey result finds that the illness rate of Parkinson's has regional disparity, so people
Some poisonous materials are there may be in suspection environment, the neuron of brain has been damaged.
3) Familial Occurrence：Physicians have found that Parkinson's seem have the tendency of Familial aggregation in long-term practice,
There is the incidence of disease of its relatives of the family of Parkinsonian higher compared with normal population.
4) genetic predisposition：Although the generation of Parkinson's is relevant with aging and environmental toxin, simultaneously not all is old
People or exposure or even are equally sucked the people of a large amount of mptp and Parkinson's can all occur with the people of same environment.Although Parkinson
Patient also has family aggregation, but does not also find clear and definite Disease-causing gene in the Parkinsonian for distributing so far,
The cause of disease for illustrating Parkinson's is multifactor.
In sum, the cause of disease of the explanation pd that any single factor can not be satisfactory.Most researchers tend to handkerchief gold
The cause of disease of gloomy disease is the above-mentioned coefficient result of each factor.I.e. after middle age, the individuality susceptible to environmental toxin is being touched
After toxin, because of its function of detoxification obstacle, there is subclinical black substance infringement, aggravate with advancing age, dopaminergic god
Through the gradual continuous dead denaturation of unit, there are the clinical symptoms of Parkinson's in final decompensation.
At present, the biochemical markers research on Parkinson's early diagnosis sets and immunology, inflammatory reaction, oxidation
Common nucleoprotein (a-Syn) the most Research Prospects of the multiple fields such as stress reaction, natural death of cerebral cells, wherein W cynapses.Histopathology is ground
Study carefully display, the common nucleoprotein abnormal aggregation of Parkinsonian's nigrostriatum cynapse, deposition and functional disturbance, and cynapse core altogether
Albumen is the main component of Lewy body, if therefore detecting cynapse core egg altogether in the body fluid such as cerebrospinal fluid, peripheral blood or saliva
Albumen, then judge that subject suffers from parkinsonism.But W albumen lacks specific and sensitive for the detection method of disease marker
Property.
Angiopoietin-like 4 albumen (ANGPTL4) is the member of the angiopoietin families of secretory protein.Angiogenin
The conservative region of family includes helical region and C-terminal fibrinogen (FBN) spline structure domain.See for example, Kim et al.,
Biochem.J.346=603-610 (2000).Other members of the family include angiogenin I, ANG2 and blood
Pipe generation element 3.Ang-1, ANG2 and 3/ angiogenin of angiogenin 4 combine Tie2 acceptors.See example
Such as, Davis et al., Ce 1187,1161-1169 (1996)；Maisonpierre et al.,Science277,55-60
(1997)；Valenzuela et al,Proc.Natl.Acad.Sc1.USA96,1904-1909(1999)；With United States Patent (USP) 5,
521,073；5,650,490；With 5,814,464.Angiogenin I and 4 is the activator of Tie2 acceptors, and ANG2
It is the antagonist (and possible activator) of Tie acceptors with 3.See for example, Folkman＆D ' Amore, Cell, 87:1153-
1155(1996)；Suri et al., Cell, 87:1171-1180(1996)；Masionpierre etal.,Science277:
55-60(1997)；With Ward＆Dumont, Seminars in Cell＆DevelopmentalBiology, 13:19-27(20
02).Tie2 acceptors belong to endothelial cell specific receptor tyrosine kinase family, and it also includes Tiel orphan receptors.The family
The protein binding Integrin ανβ3 of another member's angiopoietin-like 3 is shown in for example, the He of US patent applications 20030215451
Camenisch et al.,J.Biol.Chem.,277(19):17281-17290(2002)。
ANGPTL4 also is known as other terms.For example, ANGPTL4 also be known as liver fibrinogen/angiogenin-
GAP-associated protein GAP (HFARP) (Kim et al., Biochem.J.346=603-610 (2000)), PPAR Y angiogenins are related
Albumen (PGAR) (Yoon, et al., Mol.CellBiol., 20:5343-5349 (2000)), and the moon purport fat that fasting is induced
The factor (fasting induced adiposefactor) (FIAF) (Kerten et al., J.Biol.Chem., 275:
28488-28493(2000))。
The in vitro and in vivo research of ANGPTL4 and it is qualitative for therapeutic agent and/or treatment provide it is valuable identification with
It was found that, the therapeutic agent and/or treatment can be used to prevent, and alleviate or correct the disease related to ANGPTL4 activity and/or expression
Or dysfunction.For example, the mouse of Study on tissue culture and genetic modification has been found to be the bioprocess related to human disease
Feature further investigation priceless instrument, the disease includes immunology, and Cancerous disease, Neurobiology, angiocarpy is raw
Thing disease, fat and other diseases.Needs find and understand many biological functions of ANGPTL4.
Therefore it is urgently to solve to find a kind of gene marker that can effectively occur in early stage i.e. diagnosable parkinsonism
Problem certainly.
The content of the invention
In one aspect of the invention, there is provided the purposes of PP1158 4 its specific antibody, it is used for system
The diagnostic reagent or kit of standby detection parkinsonism.
The present invention additionally provides a kind of method for identifying relation between PP1158 4 and parkinsonism.
The present invention additionally provides a kind of antibody of PP1158 4, ABB：The weight chain variable district of the antibody is such as
SEQ ID NO：Shown in 1, the light chain variable district such as SEQ ID NO of the antibody：Shown in 2.
The present invention additionally provides the antibody of the improved PP1158 4 with enhanced binding characteristic, its point
It is not：
ABB1：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 3, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 4.
ABB2：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 5, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 6.
ABB3：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 7, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 8.
ABB4：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 9, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 10.
ABB5：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 11, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 12.
ABB6：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 13, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 14.
ABB7：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 15, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 16.
ABB8：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 17, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 18.
ABB9：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 19, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 20.
ABB10：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 21, the light chain variable district of the antibody is such as
SEQ ID NO：Shown in 22.
ABB11：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 23, the light chain variable district of the antibody is such as
SEQ ID NO：Shown in 24.
The present invention is detected using screening technique to parkinsonism first, test result indicate that angiogenin
There is obvious up-regulated expression in parkinsonism in sample albumen 4.
In addition, expression of the present invention to PP1158 4 in parkinson's syndrome patient blood is determined
Amount detection.Research confirms that PP1158 4 can be as the diagnosis marker of parkinson's syndrome, while can also make
To prevent and treat the medicine of parkinson's syndrome.
Beneficial effect:The present invention is screened by lot of experiments, test result indicate that PP1158 4 is in handkerchief
There is obvious up-regulated expression in the gloomy syndrome of gold, can be used as parkinson's syndrome disease clinical diagnosis mark.And the present invention grinds
Study carefully result and show that the expression by detecting PP1158 4 can be parkinson's syndrome preventive assessment or therapeutic scheme.
Brief description of the drawings
Fig. 1 is the statistical analysis figure of the concentration of ANGPTL4 in blood samples of patients and healthy control group blood.★ refers to P<0.05.
Fig. 2 is specificity and the sensitivity of ROC curve display protein diagnostic parkinsonism.
Specific embodiment
The specific embodiment that the present invention is provided is elaborated below in conjunction with the accompanying drawings.
Embodiment 1
Compared by the batch of early stage genomic data, by 50 normal persons and 40 protein expression data of patient point
Analysis, it is found by the applicant that ANGPTL4 albumen is overexpression in disturbances in patients with Parkinson disease.
The expression of mRNA and albumen in all patients and normal population blood is detected by the method for quantitative PCR, is led to
Cross measurement result as shown in table 1 below：
| MRNA (relative expression quantity) | Protein concentration (ng/mL) | |
| Patient | 1.7 | 110.2 |
| Normal population | 1 | 40.5 |
The above results show that ANGPTL4 high level expressions in the blood of parkinsonism patient point out ANGPTL4
Expression it is closely related with the course of disease of disturbances in patients with Parkinson disease.
ANGPTL4 concentration and disease association in the serum of embodiment 2
Using the monoclonal antibody ABB (weight chain variable district of the antibody such as SEQ ID NO of anti-ANGPTL4：Shown in 1, institute
State the light chain variable district such as SEQ ID NO of antibody：Shown in 2), 100 handkerchiefs have detected by ELISA method (double antibody sandwich method)
The concentration of ANGPTL4 in golden gloomy syndrome patient and 40 healthy control group serum.Result shows, in patients serum
The concentration of ANGPTL4 is 110.4 ± 15.3ng/ml (average ± SD)；The concentration of ANGPTL4 is in healthy control group serum
40.6 ± 10.2ng/ml (average ± SD)；ANFPRL4 concentration is apparently higher than control group serum (P ＜ 0.05) in patients serum,
Referring to Fig. 1.
In addition, being 10.25ng/ml, its sensitiveness and spy according to the cut-off values that Fig. 2 ROC curves set ANGPTL4
The opposite sex is all higher than 90%, and positive rate is 92.5% (37/40).Statistic analysis result shows that ANGPTL4 concentration is golden with handkerchief in blood
Gloomy patient is closely related, neutralizes above-mentioned experimental study, it can be deduced that conclusion, secretory ANGPTL4 high scores in disturbances in patients with Parkinson disease
Secrete, the particularly preferred mark that can be distinguished as parkinsonism and normal population.
The preparation of the kit of embodiment 3
Reagent preparation box, wherein antibody are the anti-monoclonal antibody ABB of mouse, label and specification.
Use above-mentioned detection kit, by ELISA method quantitative determination unknown blood sample (80,40 is normal population,
40 be disturbances in patients with Parkinson disease) in ANGPTL4 content.
When positive threshold value takes 102.5ng/mL, there are 38 evaluating samples for disturbances in patients with Parkinson disease, wherein 38 by verifying,
Patient is, illustrates that accuracy is very high.
When positive threshold value takes 130ng/mL, there are 39 evaluating samples for disturbances in patients with Parkinson disease, wherein 39 by verifying,
It is patient, illustrates that accuracy is more increased.
Improvement of the embodiment 4 for antibody performance
By experiment, screening, inventor obtains 10 new antibody, and antibody binding domain or its fragment can be according to
The sequence known is produced using method known to those skilled in the art.The affinity of described antibody is entered by radioimmunoassays
Row is determined.The sequence of the antibody is as follows respectively：
ABB：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 1, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 2.
ABB1：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 3, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 4.
ABB2：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 5, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 6.
ABB3：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 7, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 8.
ABB4：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 9, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 10.
ABB5：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 11, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 12.
ABB6：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 13, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 14.
ABB7：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 15, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 16.
ABB8：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 17, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 18.
ABB9：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 19, the light chain variable district such as SEQ of the antibody
ID NO：Shown in 20.
ABB10：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 21, the light chain variable district of the antibody is such as
SEQ ID NO：Shown in 22.
ABB11：The weight chain variable district of the antibody such as SEQ ID NO：Shown in 23, the light chain variable district of the antibody is such as
SEQ ID NO：Shown in 24.
| Antibody Designation | Equilibrium associations constant |
| ABB | 3.23×10-8M |
| ABB1 | 2.21×10-10M |
| ABB2 | 3.02×10-10M |
| ABB3 | 3.37×10-10M |
| ABB4 | 2.51×10-10M |
| ABB5 | 2.40×10-10M |
| ABB6 | 3.01×10-10M |
| ABB7 | 1.96×10-10M |
| ABB8 | 2.22×10-10M |
| ABB9 | 2.05×10-10M |
| ABB10 | 2.57×10-10M |
| ABB11 | 6.33×10-9M |
As can be seen from the above table, the affinity of the new antibody for providing is of about 10-10M, with more preferable affinity.
The antibody is used into identical kit in embodiment 3 to prepare, corresponding antibody is replaced respectively, sent out by testing
It is existing, identical Detection results are fully achieved, and also the concentration of antibody all reduces 20% accordingly, can equally reach
Identical using effect, this is also illustrated, described antibody activity is improved compared with original antibodies activity.
The preferred embodiments of the present invention are these are only, is not intended to limit the invention, for those skilled in the art
For member, all any modification, equivalent substitution and improvements done within the spirit and principles in the present invention etc. should be included in this
Within the protection domain of invention.
Sequence table
The ＞ Shens winters of ＜ 110 are prosperous
A kind of kits for parkinsonism detection of the ＞ of ＜ 120
〈210〉1
〈211〉138
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGlyValLeuSerGluValGlnLeuGlnGlnS
erGlyProGluLeuMetLysProGlyAlaSerValLysMetSerCysArgThrSerGlyTyrThrThrPheThrAsp
TyrSerIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleGlyTyrIleAsnProTyrAsnGlyAs
pThrTyrCysAspGlnAsnPheLysGlyLysAlaThrLeuThrPheAsnLysAlaSerSerThrAlaTyrMetGluI
leProArgLeuThrSerAspAspSerAlaValTyrTyrCysThrArgTrpLysThrIleGlnAlaProPheAlaTyr
TrpGlyGlnGlyThrLeuValThrValSerAla
〈210〉2
〈211〉129
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleG
lnMetThrGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAsp
IleValLysAsnLeuAsnTrpTyrGlnGlnLysProGlyLysProProSerPheLeuIleHisTyrAlaThrGluLe
uAlaGluGlyValProSerArgPheSerGlySerGlySerGlySerAspTyrSerLeuThrIleSerAsnLeuGluS
erGluAspPheAlaAspTyrTyrCysLeuGlnSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGlu
IleAsn
〈210〉3
〈211〉138
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB1
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAsnGlyValLeuSerGluValGlnAsnGlnGlnS
erGlyProGluLeuMetLysProGlyAlaSerValLysMetSerCysArgThrSerGlyTyrThrThrPheThrAsp
TyrSerIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleGlyGlyIleAsnAsnTyrAsnGlyAs
pThrTyrCysAsnGlnAsnPheLysGlyLysAlaThrLeuThrPheAsnLysAlaSerSerThrAlaTyrMetGluI
leProArgLeuThrSerAspAspSerAlaValPheGlyCysThrArgGlyLysThrIleGlnAlaProPheAlaTyr
TrpGlyGlnGlyThrLeuPheThrValSerAla
〈210〉4
〈211〉129
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB1
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheAspGlyAlaArgCysGluIleG
lnMetThrGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAsp
IleValLysAsnLeuAsnAspTyrGlnGlnLysProGlyLysProProSerPheLeuIleHisTyrAlaThrGluLe
uAlaGluGlyValProSerArgPheSerSerSerGlySerGlySerAspTyrSerLeuThrIleSerAsnLeuGluS
erGluAspPheAlaAspTyrTyrCysLeuSerSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGlu
IleAsn
〈210〉5
〈211〉138
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB2
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGlyIleLeuSerGluValGlnLeuIleGlnS
erGlyProGluLeuMetLysProGlyAlaSerValLysMetSerCysArgThrSerGlyTyrThrThrPheThrAsp
TyrSerIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleIleTyrIleAsnProTyrIleGlyAs
pThrTyrCysAspGlnAsnPheLysGlyLysAlaThrLeuThrPheAsnLysAlaSerSerThrAlaTyrMetGluI
leIleArgLeuThrSerAspAspSerAlaValTyrIleCysThrArgTrpLysThrIleGlnAlaProPheAlaTyr
TrpGlyGlnGlyThrLeuValThrValSerAla
〈210〉6
〈211〉129
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB2
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleG
lnMetThrAlaSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAsp
IleValLysAsnLeuAsnAlaTyrGlnGlnLeuProGlyLysProProSerPheLeuIleHisTyrAlaThrGluLe
uAlaGluGlyValProSerArgPheSerGlySerGlySerGlySerAspTyrSerLeuThrIleSerAsnLeuGluS
erGluAspPheAlaAspTyrTyrCysLeuGlnSerTyrLeuPheProTyrThrPheGlyGlyGlyThrLysLeuGlu
IleAsn
〈210〉7
〈211〉138
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB3
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGlyValLeuSerTrpValGlnLeuGlnGlnS
erGlyProGluLeuMetLysProTrpAlaSerValLysMetSerCysArgThrSerTrpTyrThrThrPheThrAsp
TyrSerIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleGlyTyrIleAsnProTyrTrpGlyAs
pThrTyrCysAspGlnAsnPheLysGlyLysAlaThrTrpThrPheAsnLysAlaTrpSerThrAlaTyrMetGluI
leProArgLeuThrSerAspAspSerTrpValTyrTyrCysThrArgTrpLysThrIleGlnAlaProPheAlaTyr
TrpGlyGlnGlyThrLeuValThrValSerAla
〈210〉8
〈211〉129
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB3
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleG
lnSerThrGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAsp
IleValLysAsnLeuAsnTrpTyrGlnGlnLysProGlyLysProProSerPheLeuIleHisTyrAlaThrGluLe
uAlaGluGlyValProSerArgPheSerGlyAspSerSerGlyAspAspTyrSerLeuThrIleSerAsnLeuGluS
erGluAspPheAlaAspTyrTyrCysLeuGlnSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGlu
IleAsn
〈210〉9
〈211〉138
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB4
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGlyValProSerGluValGlnLeuGlnGlnS
erGlyProGluLeuMetLysProGlyAlaSerValLysMetSerCysArgThrSerGlyTyrThrThrPheThrAsp
TyrSerIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleGlyTyrIleAsnProTyrAsnGlyAs
pThrTyrCysAspGlnAsnPheLysGlyLysAlaThrLeuProPheAsnLysAlaSerProThrAlaTyrMetGluI
leProArgLeuThrSerAspAspSerProValTyrTyrCysThrProTrpLysThrIleGlnAlaProPheAlaTyr
TrpGlyGlnGlyProLeuValThrValSerAla
〈210〉10
〈211〉129
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB4
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleG
lnMetThrGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAsp
IleValLysAsnLeuAsnLeuTyrGlnGlnSerProGlyLysProProSerPheLeuIleHisTyrAlaSerGluLe
uAlaGluGlyValProLeuArgPheSerGlySerGlySerGlySerAspTyrSerLeuThrIleSerAsnLeuGluS
erGluAspPheAlaAspTyrTyrCysLeuGlnSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGlu
IleAsn
〈210〉11
〈211〉138
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB5
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGluValLeuSerGluValGlnLeuGlnGlnS
erGlyProGluLeuMetLysGluGlyAlaSerValLysMetSerCysArgThrSerGlyTyrThrThrPheThrGlu
TyrSerIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleGlyTyrIleAsnProTyrAsnGlyAs
pThrTyrCysAspGlnAsnPheLysGlyLysAlaThrLeuGluPheAsnLysAlaSerSerThrAlaTyrMetGluI
leProArgLeuThrSerAspAspSerAlaValTyrTyrCysThrArgTrpGluThrIleGlnAlaProPheAlaTyr
TrpGlyGlnGlyThrLeuValThrValSerAla
〈210〉12
〈211〉129
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB5
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleG
lnAlaThrGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAsp
IleValLysAsnLeuAsnTrpTyrGlnGlnLysProGlyLysProProSerPheLeuIleHisTyrAlaThrGluLe
uAlaGluGlyValAlaSerArgPheSerGlySerGlySerGlySerAspTyrSerLeuThrIleSerAsnLeuGluS
erGluAspPheAlaAspTyrTyrCysSerGlnSerTyrAspPheProTyrThrPheAlaGlyGlyThrLysLeuGlu
IleAsn
〈210〉13
〈211〉138
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB6
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrCysGlyValLeuSerGluCysGlnLeuGlnGlnS
erGlyProGluLeuMetLysProGlyAlaSerValLysMetSerCysArgThrSerGlyTyrThrThrPheThrAsp
TyrSerIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleCysTyrIleAsnCysTyrAsnGlyAs
pThrTyrCysAspGlnAsnPheLysGlyLysAlaThrLeuThrPheAsnLysAlaSerSerThrAlaTyrMetGluI
leCysArgLeuThrSerAspAspSerAlaCysTyrTyrCysThrArgTrpLysThrIleGlnAlaProPheAlaTyr
TrpGlyGlnGlyThrLeuValThrValSerAla
〈210〉14
〈211〉129
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB6
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleG
lnMetThrIleSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAsp
IleValLysAsnLeuAsnTrpTyrGlnGlnLysProGlyLysIleProSerPheLeuIleHisTyrAlaThrGluLe
uAlaGluGlyValProSerArgPheSerGlySerProSerGlySerAspTyrSerLeuThrIleSerAsnLeuGluS
erGluAspPheAlaAspTyrTyrIleLeuGlnSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGlu
IleAsn
〈210〉15
〈211〉138
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB7
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGlyValLeuGlyGluValGlnLeuGlnGlnS
erGlyProGluLeuMetLysProGlyAlaSerValLysMetGlyCysArgThrSerGlyTyrThrThrPheThrAsp
TyrSerIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpGlyGlyTyrIleAsnProTyrAsnGlyAs
pThrTyrCysAspGlnAsnPheLysGlyLysAlaThrLeuThrPheAsnLysAlaSerGlyThrAlaTyrMetGluI
leProArgLeuThrSerAspAspSerAlaValTyrTyrCysThrArgTrpLysThrIleGlnAlaProPheAlaTyr
TrpGlyGlnGlyThrLeuValThrValSerAla
〈210〉16
〈211〉129
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB7
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleA
spMetThrGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAsp
IleValLysAsnLeuAsnTrpTyrGlnGlnLysProGlyLysProProSerPheLeuIleHisTyrAspThrGluLe
uAlaGluAspValProSerArgPheSerSerSerGlySerGlySerAspTyrSerLeuThrIleSerAsnLeuGluS
erGluAspPheAlaAspTyrTyrCysLeuGlnSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGlu
IleAsn
〈210〉17
〈211〉138
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB8
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGlyValLeuSerGluValGlnLeuGlnArgS
erGlyProGluLeuMetLysProGlyAlaSerValLysMetSerCysArgArgSerGlyTyrThrThrPheThrAsp
TyrSerIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleGlyTyrIleAsnProTyrArgGlyAs
pThrTyrCysAspGlnAsnPheLysGlyLysAlaThrArgThrPheAsnLysAlaSerSerThrAlaTyrMetGluI
leProArgLeuThrSerAspAspSerAlaArgTyrTyrCysThrArgTrpArgThrIleGlnAlaProPheAlaTyr
TrpGlyGlnGlyThrLeuValThrValSerAla
〈210〉18
〈211〉129
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB8
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheAsnGlyAlaArgCysGluIleG
lnMetThrGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAsp
IleValLysAsnLeuAsnIleTyrGlnGlnLysAsnGlyLysProProSerPheLeuIleHisTyrAlaThrGluLe
uAlaGluGlyValProSerArgPheAsnGlySerGlySerGlySerAspTyrSerLeuThrIleSerAsnLeuGluS
erAsnAspPheAlaAspTyrTyrCysLeuIleSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGlu
IleAsn
〈210〉19
〈211〉138
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB9
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrTrpGlyValLeuSerGluValGlnLeuGlnGlnS
erGlyProGluLeuMetLysProGlyAlaSerValLysMetSerCysArgThrSerGlyTyrThrThrPheThrAsp
TyrTrpIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleGlyTyrIleAsnProTyrAsnGlyAs
pThrTyrCysAspGlnAsnPheLysGlyLysAlaThrLeuTrpPheAsnLysAlaSerSerThrAlaTyrMetGluT
rpProArgLeuThrSerAspAspSerAlaValTyrTyrCysThrArgTrpLysThrIleGlnAlaProPheAlaTyr
TrpGlyGlnGlyThrLeuValThrValSerAla
〈210〉20
〈211〉129
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB9
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleG
lnMetThrGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaLeuGlnAsp
IleValLysAsnLeuLeuTrpTyrGlnGlnLysProGlyLysProProSerPheLeuIleGlyTyrAlaThrGluLe
uAlaGluGlyValProSerArgPheLeuGlySerGlyLeuGlySerAspTyrSerLeuThrIleSerAsnLeuGluS
erGluAspPheAlaAspTyrTyrCysLeuGlnSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGlu
IleAsn
〈210〉21
〈211〉138
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB10
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGlyValLeuSerAlaValGlnLeuGlnGlnS
erGlyProGluLeuMetLysProGlyAlaSerValLysMetSerCysAlaThrSerGlyTyrThrThrPheThrAsp
TyrSerIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleGlyTyrIleAsnProAlaAsnGlyAs
pThrTyrCysAspGlnAsnPheLysGlyLysAlaThrLeuThrPheAsnLysAlaSerSerThrAlaTyrMetGluI
leProArgLeuThrSerAspAspSerAlaSerTyrTyrCysThrArgTrpLysThrIleGlnAlaProPheAlaTyr
TrpGlyGlnGlyThrLeuValThrValSerAla
〈210〉22
〈211〉129
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB10
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleG
lnMetGluGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysAsnAlaThrGlnAsp
IleValLysAsnLeuAsnTrpTyrGlnGlnLysProGlyLysProProSerPheLeuIleHisTyrAlaThrGluLe
uAlaAsnGlyValProSerArgPheSerGluSerGlyGluGlySerAspTyrSerLeuThrIleSerAsnLeuGluS
erGluAspPheAlaAspTyrTyrCysLeuGlnSerTyrAsnPheProTyrThrPheGlyGlyGlyThrLysLeuGlu
IleAsn
〈210〉23
〈211〉138
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB11
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGlyValLeuSerGluValGlnGlyGlnGlnS
erGlyProGluLeuMetLysProGlyAlaSerValLysMetSerCysArgThrSerGlyTyrThrThrPheThrAsp
TyrGlyIleHisTrpValLysGlnSerHisGlyLysArgLeuMetTrpIleGlyTyrIleAsnProTyrAsnGlyAs
pThrTyrCysAspGlnAsnPheLysGlyLysAlaThrLeuThrPheAsnLysAlaSerSerThrAlaTyrMetGluI
leProArgLeuThrSerAspAspSerAlaValTyrMetCysThrArgTrpLysThrIleGlnAlaProPheAlaTyr
TrpGlyGlnGlyThrLeuValThrValSerAla
〈210〉24
〈211〉129
〈212〉PRT
The ＞ artificial sequences of ＜ 213
〈400〉ABB11
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuGlyLeuTrpPheProGlyAlaArgCysGluIleG
lnMetProGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnGlyThrGlnAsp
IleValLysAsnLeuAsnTrpTyrGlnGlnLysProGlyLysProProSerPheLeuIleHisTyrAlaThrGluLe
uAlaGluGlyValProSerArgPheSerGlySerGlySerGlySerAspTyrSerLeuThrIleSerAsnLeuGluS
erGluAspPheAlaAspTyrTyrCysProGlnSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGlu
IleAsn
Claims (5)
1. it is a kind of for parkinsonism detection kit, it is characterised in that：It contains being capable of specific detection Parkinson
The monoclonal antibody of syndrome.
2. kit as claimed in claim 1, it is characterised in that：The monoclonal antibody can specifically bind ANGPTL4.
3. kit as claimed in claim 2, it is characterised in that：The weight chain variable district of wherein described antibody is respectively such as SEQ
ID NO：1st, shown in 3,5,7,9,11,13,15,17,19,21,23；The corresponding light chain variable district of the antibody is successively such as SEQ ID
NO：2nd, shown in 4,6,8,10,12,14,16,18,20,22,24.
4. a kind of monoclonal antibody, it is characterised in that：The weight chain variable district of the antibody is respectively such as SEQ ID NO：1、3、5、7、
9th, shown in 11,13,15,17,19,21,23；The corresponding light chain variable district of the antibody is successively such as SEQ ID NO：2、4、6、8、
10th, shown in 12,14,16,18,20,22,24.
5. application of the monoclonal antibody described in claim 4 in the kit for preparing detection parkinsonism.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710113949.6A CN106706930B (en) | 2017-02-28 | 2017-02-28 | A kind of kit for parkinsonism detection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710113949.6A CN106706930B (en) | 2017-02-28 | 2017-02-28 | A kind of kit for parkinsonism detection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106706930A true CN106706930A (en) | 2017-05-24 |
| CN106706930B CN106706930B (en) | 2018-11-02 |
Family
ID=58917650
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|---|---|---|---|
| CN201710113949.6A Active CN106706930B (en) | 2017-02-28 | 2017-02-28 | A kind of kit for parkinsonism detection |
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| Country | Link |
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| CN (1) | CN106706930B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101370525A (en) * | 2005-08-19 | 2009-02-18 | 艾博特公司 | Dual variable domain immunoglobin and uses thereof |
| CN102692500A (en) * | 2011-03-21 | 2012-09-26 | 上海市肿瘤研究所 | ANGPTL4 as a marker of liver cancer metastasis by serological detection and application thereof |
-
2017
- 2017-02-28 CN CN201710113949.6A patent/CN106706930B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101370525A (en) * | 2005-08-19 | 2009-02-18 | 艾博特公司 | Dual variable domain immunoglobin and uses thereof |
| CN102692500A (en) * | 2011-03-21 | 2012-09-26 | 上海市肿瘤研究所 | ANGPTL4 as a marker of liver cancer metastasis by serological detection and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106706930B (en) | 2018-11-02 |
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Address after: 225000 South Park Chuangfu Workshop Building 4-2, Yangzhou High-tech Industrial Development Zone, Jiangsu Province, 4 and 5 floors (Hanjiang Economic Development Zone 4) Patentee after: Jiangsu nuomingzhe natural medicine laboratory Co.,Ltd. Address before: 225128 Floors 4 and 5 of Nanyuan Chuangfu Workshop Building 4-2, Yangzhou High-tech Industrial Development Zone, Jiangsu Province (Yongjiang Economic Development Zone 4) Patentee before: YANGZHOU NUOMING ZHETIAN MEDICAL LABORATORY Co.,Ltd. |