CN106706930B - A kind of kit for parkinsonism detection - Google Patents
A kind of kit for parkinsonism detection Download PDFInfo
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- G—PHYSICS
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- 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
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- 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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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
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- G01N2333/515—Angiogenesic factors; Angiogenin
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- 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
This application involves a kind of kits for parkinsonism detection.The kit includes to be capable of the antibody of specific detection parkinsonism, and antibody therein has preferable binding constant, has better detection accuracy than the kit of the prior art.
Description
Technical field
The present invention relates to detection fields, and in particular to a kind of kit for parkinsonism detection.
Background technology
Parkinson's disease (PD) also known as shaking plasy are one of most common neurodegenerative diseases.Epidemiology is shown, is suffered from
Sick rate is 15~3,28/,100,000 populations, 65 years old crowd of > about 1%；Incidence 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, may be related with social factor, drug factors, patients factors etc..PD pathological changes are：Substantia nigra of midbrain causes
Compact part, Neurons of Locus Coeruleus depigmentation, black substance pigment is thin out and Lewy body occurs.PD nerve biochemical changes are：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 acted on the acetylcholine of DA function antagonisms (ACH) in nigrostriatum system it is relatively hyperfunction, DA with
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 related.
1) age ageing：
2) environmental factor：Epidemiological survey as a result, it has been found that, there are regional disparities for the illness rate of Parkinson's disease, so people
Suspect in environment there may be some toxic substances, has damaged the neuron of brain.
3) Familial Occurrence：Physicians have found that Parkinson's disease seems there is Familial aggregation in long-term practice,
There is the incidence of its relatives of the family of Parkinsonian higher compared with normal population.
4) genetic predisposition：Although the generation of Parkinson's disease is related with aging and environmental toxin, and not all old age
People or exposure are in the people of same environment, or even Parkinson's disease can occur in the people for equally sucking a large amount of mptp.Although Parkinson
Patient also has family aggregation, but does not also find specific Disease-causing gene in the Parkinsonian distributed so far,
Illustrate that the cause of disease of Parkinson's disease is multifactor.
In conclusion any single factor cannot be satisfactory explanation pd the cause of disease.Most researchers tend to pa gold
The cause of disease of gloomy disease is the above-mentioned coefficient result of each factor.I.e. after middle age, the individual susceptible to environmental toxin is touching
After toxin, because of its function of detoxification obstacle, there is subclinical black substance damage, aggravate with advancing age, dopaminergic god
Through the gradual continuous dead denaturation of member, there are the clinical symptoms of Parkinson's disease in final decompensation.
Currently, the biochemical markers research about Parkinson's disease early diagnosis is set and immunology, inflammatory reaction, oxidation
The multiple fields such as stress reaction, natural death of cerebral cells, wherein W cynapses are total to nucleoprotein (a-Syn) most Research Prospects.Histopathology is ground
Study carefully display, Parkinsonian's nigrostriatum cynapse is total to nucleoprotein abnormal aggregation, deposition and functional disturbance, and cynapse is total to core
Albumen is the main component of Lewy body, if therefore detecting that cynapse is total to core egg in the body fluid such as cerebrospinal fluid, peripheral blood or saliva
Albumen then judges that subject suffers from parkinsonism.But the detection method shortage that W albumen is disease marker is specific and sensitive
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, angiopoietin 2 and blood
Pipe generates element 3.Ang-1, angiopoietin 2 and 3/ angiogenin 4 of angiogenin combine Tie2 receptors.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 agonist of Tie2 receptors, and angiopoietin 2
It is the antagonist (and possible agonist) of Tie receptors 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 receptors belong to endothelial cell specific receptor tyrosine kinase family, also include Tiel orphan receptors.The family
3 protein binding Integrin ανβ3 of another member's angiopoietin-like is shown in for example, 20030215451 He of US patent applications
Camenisch et al.,J.Biol.Chem.,277(19):17281-17290(2002)。
ANGPTL4 also is known as other terms.For example, ANGPTL4 also is 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 fasting induction moon purport fat
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 and
It was found that the therapeutic agent and/or treatment can be used for preventing, alleviates or correct and ANGPTL4 activity and/or the relevant disease of expression
Or dysfunction.For example, the mouse of Study on tissue culture and genetic modification have been found be and the relevant bioprocess of human disease
Functional further investigation priceless tool, the disease includes immunology, Cancerous disease, Neurobiology, and angiocarpy is raw
Object disease, fat and other diseases.Need to find and understand many biological functions of ANGPTL4.
Therefore it can be effectively urgently to solve in the gene marker of early stage i.e. diagnosable parkinsonism generation to find a kind of
Certainly the problem of.
Invention content
In one aspect of the invention, the purposes for providing 4 its specific antibody of angiopoietin-like protein be used to make
The diagnostic reagent or kit of standby detection parkinsonism.
The present invention additionally provides a kind of methods of relationship between identification angiopoietin-like protein 4 and parkinsonism.
The present invention additionally provides a kind of antibody of angiopoietin-like protein 4, ABB：The heavy chain variable region of the antibody is such as
SEQ ID NO：Shown in 1, the light chain variable region such as SEQ ID NO of the antibody：Shown in 2.
The present invention additionally provides it is improved have enhancing binding characteristic angiopoietin-like protein 4 antibody, point
It is not：
ABB1：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 3, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 4.
ABB2：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 5, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 6.
ABB3：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 7, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 8.
ABB4：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 9, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 10.
ABB5：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 11, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 12.
ABB6：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 13, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 14.
ABB7：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 15, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 16.
ABB8：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 17, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 18.
ABB9：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 19, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 20.
ABB10：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 21, the light chain variable region of the antibody is such as
SEQ ID NO：Shown in 22.
ABB11：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 23, the light chain variable region of the antibody is such as
SEQ ID NO：Shown in 24.
The present invention first detects parkinsonism using screening technique, the experimental results showed that angiogenin
There is apparent up-regulated expression in parkinsonism in sample albumen 4.
In addition, the present invention determines expression of the angiopoietin-like protein 4 in parkinson's syndrome patient blood
Amount detection.Research confirms that angiopoietin-like protein 4 can be as the diagnosis marker of parkinson's syndrome, while can also make
To prevent the drug of parkinson's syndrome.
Advantageous effect:The present invention is screened by lot of experiments, the experimental results showed that angiopoietin-like protein 4 is in pa
There is apparent up-regulated expression in the gloomy syndrome of gold, can be used as parkinson's syndrome disease clinical diagnosis marker.And the present invention is ground
Study carefully the result shows that can be parkinson's syndrome preventive assessment or therapeutic scheme by the expression for detecting angiopoietin-like protein 4.
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 that ROC curve shows protein diagnostic parkinsonism.
Specific implementation mode
It elaborates below in conjunction with the accompanying drawings to specific implementation mode provided by the invention.
Embodiment 1
It is compared by the batch of genomic data early period, passes through the protein expression data of 50 normal persons and 40 patients 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 are detected by the method for quantitative PCR, are led to
It is as shown in table 1 below to cross measurement result：
| MRNA (relative expression quantity) | Albumen concentration (ng/mL) | |
| Patient | 1.7 | 110.2 |
| Normal population | 1 | 40.5 |
The above results show ANGPTL4 high level expressions in the blood of parkinsonism patient, prompt ANGPTL4
Expression and disturbances in patients with Parkinson disease the course of disease it is closely related.
ANGPTL4 concentration and disease association in 2 serum of embodiment
Using the monoclonal antibody ABB (heavy chain variable region of the antibody such as SEQ ID NO of anti-ANGPTL4：Shown in 1, institute
State the light chain variable region such as SEQ ID NO of antibody：Shown in 2), 100 pas are had detected by ELISA method (double antibody sandwich method)
The concentration of ANGPTL4 in golden gloomy syndrome patient and 40 healthy control group serum.The result shows that in patients serum
A concentration of 110.4 ± 15.3ng/ml (average ± SD) of ANGPTL4；ANGPTL4's is a concentration of 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, the cut-off values that ROC curve sets ANGPTL4 according to fig. 2 are 10.25ng/ml, sensibility and spy
The opposite sex is all higher than 90%, and positive rate is 92.5% (37/40).Statistic analysis result shows that ANGPTL4 concentration and pa are golden 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
It secretes, the particularly preferred marker that can be distinguished as parkinsonism and normal population.
The preparation of 3 kit of embodiment
Reagent preparation box, wherein antibody are the anti-monoclonal antibody ABB of mouse, label and specification.
With above-mentioned detection kit, quantitatively had detected by ELISA method unknown blood sample (80,40 are normal population,
40 be disturbances in patients with Parkinson disease) in ANGPTL4 content.
When positive threshold value takes 102.5ng/mL, it is disturbances in patients with Parkinson disease to have 38 evaluating samples, wherein 38 through and verifications,
It is patient, illustrates that accuracy is very high.
When positive threshold value takes 130ng/mL, it is disturbances in patients with Parkinson disease to have 39 evaluating samples, wherein 39 are passed through and verified,
For patient, illustrate that accuracy is more increased.
Embodiment 4 is directed to the improvement of antibody performance
By experiment, screening, inventor obtains 10 new antibody, and antibody binding domain or its segment can be according to
The sequence known is generated using method known to those skilled in the art.The affinity of the antibody by radioimmunoassays into
Row measures.The sequence difference of the antibody is as follows：
ABB：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 1, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 2.
ABB1：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 3, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 4.
ABB2：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 5, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 6.
ABB3：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 7, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 8.
ABB4：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 9, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 10.
ABB5：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 11, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 12.
ABB6：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 13, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 14.
ABB7：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 15, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 16.
ABB8：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 17, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 18.
ABB9：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 19, the light chain variable region such as SEQ of the antibody
ID NO：Shown in 20.
ABB10：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 21, the light chain variable region of the antibody is such as
SEQ ID NO：Shown in 22.
ABB11：The heavy chain variable region of the antibody such as SEQ ID NO：Shown in 23, the light chain variable region 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 antibody newly provided is about 10-10M has better affinity.
The antibody is prepared for identical kit in embodiment 3, corresponding antibody is replaced respectively, is sent out by testing
It is existing, identical detection result is fully achieved, and the use concentration of antibody all reduces 20% accordingly, can equally reach
Identical using effect, this also illustrates, the antibody activity is improved compared with original antibodies activity.
It these are only the preferred embodiment of the present invention, be not intended to restrict the invention, for those skilled in the art
For member, any modification, equivalent substitution, improvement and etc. done all within the spirits and principles of the present invention should be included in this
Within the protection domain of invention.
Sequence table
110 Shens the > winters of < are prosperous
A kind of kits for parkinsonism detection of 120 > of <
〈210〉1
〈211〉138
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGlyValLeuSerGluValGlnLeuGlnGlnSerGl
yProGluLeuMetLysProGlyAlaSerValLysMetSerCysArgThrSerGlyTyrThrThrPheThrAspTyrS
erIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleGlyTyrIleAsnProTyrAsnGlyAspThr
TyrCysAspGlnAsnPheLysGlyLysAlaThrLeuThrPheAsnLysAlaSerSerThrAlaTyrMetGluIlePr
oArgLeuThrSerAspAspSerAlaValTyrTyrCysThrArgTrpLysThrIleGlnAlaProPheAlaTyrTrpG
lyGlnGlyThrLeuValThrValSerAla
〈210〉2
〈211〉129
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleGlnMe
tThrGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAspIleV
alLysAsnLeuAsnTrpTyrGlnGlnLysProGlyLysProProSerPheLeuIleHisTyrAlaThrGluLeuAla
GluGlyValProSerArgPheSerGlySerGlySerGlySerAspTyrSerLeuThrIleSerAsnLeuGluSerGl
uAspPheAlaAspTyrTyrCysLeuGlnSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGluIleA
sn
〈210〉3
〈211〉138
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB1
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAsnGlyValLeuSerGluValGlnAsnGlnGlnSerGl
yProGluLeuMetLysProGlyAlaSerValLysMetSerCysArgThrSerGlyTyrThrThrPheThrAspTyrS
erIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleGlyGlyIleAsnAsnTyrAsnGlyAspThr
TyrCysAsnGlnAsnPheLysGlyLysAlaThrLeuThrPheAsnLysAlaSerSerThrAlaTyrMetGluIlePr
oArgLeuThrSerAspAspSerAlaValPheGlyCysThrArgGlyLysThrIleGlnAlaProPheAlaTyrTrpG
lyGlnGlyThrLeuPheThrValSerAla
〈210〉4
〈211〉129
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB1
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheAspGlyAlaArgCysGluIleGlnMe
tThrGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAspIleV
alLysAsnLeuAsnAspTyrGlnGlnLysProGlyLysProProSerPheLeuIleHisTyrAlaThrGluLeuAla
GluGlyValProSerArgPheSerSerSerGlySerGlySerAspTyrSerLeuThrIleSerAsnLeuGluSerGl
uAspPheAlaAspTyrTyrCysLeuSerSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGluIleA
sn
〈210〉5
〈211〉138
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB2
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGlyIleLeuSerGluValGlnLeuIleGlnSerGl
yProGluLeuMetLysProGlyAlaSerValLysMetSerCysArgThrSerGlyTyrThrThrPheThrAspTyrS
erIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleIleTyrIleAsnProTyrIleGlyAspThr
TyrCysAspGlnAsnPheLysGlyLysAlaThrLeuThrPheAsnLysAlaSerSerThrAlaTyrMetGluIleIl
eArgLeuThrSerAspAspSerAlaValTyrIleCysThrArgTrpLysThrIleGlnAlaProPheAlaTyrTrpG
lyGlnGlyThrLeuValThrValSerAla
〈210〉6
〈211〉129
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB2
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleGlnMe
tThrAlaSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAspIleV
alLysAsnLeuAsnAlaTyrGlnGlnLeuProGlyLysProProSerPheLeuIleHisTyrAlaThrGluLeuAla
GluGlyValProSerArgPheSerGlySerGlySerGlySerAspTyrSerLeuThrIleSerAsnLeuGluSerGl
uAspPheAlaAspTyrTyrCysLeuGlnSerTyrLeuPheProTyrThrPheGlyGlyGlyThrLysLeuGluIleA
sn
〈210〉7
〈211〉138
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB3
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGlyValLeuSerTrpValGlnLeuGlnGlnSerGl
yProGluLeuMetLysProTrpAlaSerValLysMetSerCysArgThrSerTrpTyrThrThrPheThrAspTyrS
erIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleGlyTyrIleAsnProTyrTrpGlyAspThr
TyrCysAspGlnAsnPheLysGlyLysAlaThrTrpThrPheAsnLysAlaTrpSerThrAlaTyrMetGluIlePr
oArgLeuThrSerAspAspSerTrpValTyrTyrCysThrArgTrpLysThrIleGlnAlaProPheAlaTyrTrpG
lyGlnGlyThrLeuValThrValSerAla
〈210〉8
〈211〉129
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB3
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleGlnSe
rThrGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAspIleV
alLysAsnLeuAsnTrpTyrGlnGlnLysProGlyLysProProSerPheLeuIleHisTyrAlaThrGluLeuAla
GluGlyValProSerArgPheSerGlyAspSerSerGlyAspAspTyrSerLeuThrIleSerAsnLeuGluSerGl
uAspPheAlaAspTyrTyrCysLeuGlnSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGluIleA
sn
〈210〉9
〈211〉138
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB4
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGlyValProSerGluValGlnLeuGlnGlnSerGl
yProGluLeuMetLysProGlyAlaSerValLysMetSerCysArgThrSerGlyTyrThrThrPheThrAspTyrS
erIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleGlyTyrIleAsnProTyrAsnGlyAspThr
TyrCysAspGlnAsnPheLysGlyLysAlaThrLeuProPheAsnLysAlaSerProThrAlaTyrMetGluIlePr
oArgLeuThrSerAspAspSerProValTyrTyrCysThrProTrpLysThrIleGlnAlaProPheAlaTyrTrpG
lyGlnGlyProLeuValThrValSerAla
〈210〉10
〈211〉129
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB4
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleGlnMe
tThrGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAspIleV
alLysAsnLeuAsnLeuTyrGlnGlnSerProGlyLysProProSerPheLeuIleHisTyrAlaSerGluLeuAla
GluGlyValProLeuArgPheSerGlySerGlySerGlySerAspTyrSerLeuThrIleSerAsnLeuGluSerGl
uAspPheAlaAspTyrTyrCysLeuGlnSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGluIleA
sn
〈210〉11
〈211〉138
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB5
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGluValLeuSerGluValGlnLeuGlnGlnSerGl
yProGluLeuMetLysGluGlyAlaSerValLysMetSerCysArgThrSerGlyTyrThrThrPheThrGluTyrS
erIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleGlyTyrIleAsnProTyrAsnGlyAspThr
TyrCysAspGlnAsnPheLysGlyLysAlaThrLeuGluPheAsnLysAlaSerSerThrAlaTyrMetGluIlePr
oArgLeuThrSerAspAspSerAlaValTyrTyrCysThrArgTrpGluThrIleGlnAlaProPheAlaTyrTrpG
lyGlnGlyThrLeuValThrValSerAla
〈210〉12
〈211〉129
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB5
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleGlnAl
aThrGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAspIleV
alLysAsnLeuAsnTrpTyrGlnGlnLysProGlyLysProProSerPheLeuIleHisTyrAlaThrGluLeuAla
GluGlyValAlaSerArgPheSerGlySerGlySerGlySerAspTyrSerLeuThrIleSerAsnLeuGluSerGl
uAspPheAlaAspTyrTyrCysSerGlnSerTyrAspPheProTyrThrPheAlaGlyGlyThrLysLeuGluIleA
sn
〈210〉13
〈211〉138
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB6
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrCysGlyValLeuSerGluCysGlnLeuGlnGlnSerGl
yProGluLeuMetLysProGlyAlaSerValLysMetSerCysArgThrSerGlyTyrThrThrPheThrAspTyrS
erIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleCysTyrIleAsnCysTyrAsnGlyAspThr
TyrCysAspGlnAsnPheLysGlyLysAlaThrLeuThrPheAsnLysAlaSerSerThrAlaTyrMetGluIleCy
sArgLeuThrSerAspAspSerAlaCysTyrTyrCysThrArgTrpLysThrIleGlnAlaProPheAlaTyrTrpG
lyGlnGlyThrLeuValThrValSerAla
〈210〉14
〈211〉129
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB6
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleGlnMe
tThrIleSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAspIleV
alLysAsnLeuAsnTrpTyrGlnGlnLysProGlyLysIleProSerPheLeuIleHisTyrAlaThrGluLeuAla
GluGlyValProSerArgPheSerGlySerProSerGlySerAspTyrSerLeuThrIleSerAsnLeuGluSerGl
uAspPheAlaAspTyrTyrIleLeuGlnSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGluIleA
sn
〈210〉15
〈211〉138
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB7
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGlyValLeuGlyGluValGlnLeuGlnGlnSerGl
yProGluLeuMetLysProGlyAlaSerValLysMetGlyCysArgThrSerGlyTyrThrThrPheThrAspTyrS
erIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpGlyGlyTyrIleAsnProTyrAsnGlyAspThr
TyrCysAspGlnAsnPheLysGlyLysAlaThrLeuThrPheAsnLysAlaSerGlyThrAlaTyrMetGluIlePr
oArgLeuThrSerAspAspSerAlaValTyrTyrCysThrArgTrpLysThrIleGlnAlaProPheAlaTyrTrpG
lyGlnGlyThrLeuValThrValSerAla
〈210〉16
〈211〉129
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB7
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleAspMe
tThrGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAspIleV
alLysAsnLeuAsnTrpTyrGlnGlnLysProGlyLysProProSerPheLeuIleHisTyrAspThrGluLeuAla
GluAspValProSerArgPheSerSerSerGlySerGlySerAspTyrSerLeuThrIleSerAsnLeuGluSerGl
uAspPheAlaAspTyrTyrCysLeuGlnSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGluIleA
sn
〈210〉17
〈211〉138
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB8
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGlyValLeuSerGluValGlnLeuGlnArgSerGl
yProGluLeuMetLysProGlyAlaSerValLysMetSerCysArgArgSerGlyTyrThrThrPheThrAspTyrS
erIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleGlyTyrIleAsnProTyrArgGlyAspThr
TyrCysAspGlnAsnPheLysGlyLysAlaThrArgThrPheAsnLysAlaSerSerThrAlaTyrMetGluIlePr
oArgLeuThrSerAspAspSerAlaArgTyrTyrCysThrArgTrpArgThrIleGlnAlaProPheAlaTyrTrpG
lyGlnGlyThrLeuValThrValSerAla
〈210〉18
〈211〉129
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB8
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheAsnGlyAlaArgCysGluIleGlnMe
tThrGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaThrGlnAspIleV
alLysAsnLeuAsnIleTyrGlnGlnLysAsnGlyLysProProSerPheLeuIleHisTyrAlaThrGluLeuAla
GluGlyValProSerArgPheAsnGlySerGlySerGlySerAspTyrSerLeuThrIleSerAsnLeuGluSerAs
nAspPheAlaAspTyrTyrCysLeuIleSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGluIleA
sn
〈210〉19
〈211〉138
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB9
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrTrpGlyValLeuSerGluValGlnLeuGlnGlnSerGl
yProGluLeuMetLysProGlyAlaSerValLysMetSerCysArgThrSerGlyTyrThrThrPheThrAspTyrT
rpIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleGlyTyrIleAsnProTyrAsnGlyAspThr
TyrCysAspGlnAsnPheLysGlyLysAlaThrLeuTrpPheAsnLysAlaSerSerThrAlaTyrMetGluTrpPr
oArgLeuThrSerAspAspSerAlaValTyrTyrCysThrArgTrpLysThrIleGlnAlaProPheAlaTyrTrpG
lyGlnGlyThrLeuValThrValSerAla
〈210〉20
〈211〉129
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB9
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleGlnMe
tThrGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnAlaLeuGlnAspIleV
alLysAsnLeuLeuTrpTyrGlnGlnLysProGlyLysProProSerPheLeuIleGlyTyrAlaThrGluLeuAla
GluGlyValProSerArgPheLeuGlySerGlyLeuGlySerAspTyrSerLeuThrIleSerAsnLeuGluSerGl
uAspPheAlaAspTyrTyrCysLeuGlnSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGluIleA
sn
〈210〉21
〈211〉138
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB10
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGlyValLeuSerAlaValGlnLeuGlnGlnSerGl
yProGluLeuMetLysProGlyAlaSerValLysMetSerCysAlaThrSerGlyTyrThrThrPheThrAspTyrS
erIleHisTrpValLysGlnSerHisGlyLysArgLeuGluTrpIleGlyTyrIleAsnProAlaAsnGlyAspThr
TyrCysAspGlnAsnPheLysGlyLysAlaThrLeuThrPheAsnLysAlaSerSerThrAlaTyrMetGluIlePr
oArgLeuThrSerAspAspSerAlaSerTyrTyrCysThrArgTrpLysThrIleGlnAlaProPheAlaTyrTrpG
lyGlnGlyThrLeuValThrValSerAla
〈210〉22
〈211〉129
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB10
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuLeuLeuTrpPheProGlyAlaArgCysGluIleGlnMe
tGluGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysAsnAlaThrGlnAspIleV
alLysAsnLeuAsnTrpTyrGlnGlnLysProGlyLysProProSerPheLeuIleHisTyrAlaThrGluLeuAla
AsnGlyValProSerArgPheSerGluSerGlyGluGlySerAspTyrSerLeuThrIleSerAsnLeuGluSerGl
uAspPheAlaAspTyrTyrCysLeuGlnSerTyrAsnPheProTyrThrPheGlyGlyGlyThrLysLeuGluIleA
sn
〈210〉23
〈211〉138
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB11
MetGlyTrpSerTrpIlePheLeuPheLeuSerGluThrAlaGlyValLeuSerGluValGlnGlyGlnGlnSerGl
yProGluLeuMetLysProGlyAlaSerValLysMetSerCysArgThrSerGlyTyrThrThrPheThrAspTyrG
lyIleHisTrpValLysGlnSerHisGlyLysArgLeuMetTrpIleGlyTyrIleAsnProTyrAsnGlyAspThr
TyrCysAspGlnAsnPheLysGlyLysAlaThrLeuThrPheAsnLysAlaSerSerThrAlaTyrMetGluIlePr
oArgLeuThrSerAspAspSerAlaValTyrMetCysThrArgTrpLysThrIleGlnAlaProPheAlaTyrTrpG
lyGlnGlyThrLeuValThrValSerAla
〈210〉24
〈211〉129
〈212〉PRT
213 > artificial sequences of <
〈400〉ABB11
MetAspMetArgAlaProAlaGlnPheLeuGlyIleLeuGlyLeuTrpPheProGlyAlaArgCysGluIleGlnMe
tProGlnSerProSerSerMetSerAlaSerLeuGlyAspArgIleThrIleThrCysGlnGlyThrGlnAspIleV
alLysAsnLeuAsnTrpTyrGlnGlnLysProGlyLysProProSerPheLeuIleHisTyrAlaThrGluLeuAla
GluGlyValProSerArgPheSerGlySerGlySerGlySerAspTyrSerLeuThrIleSerAsnLeuGluSerGl
uAspPheAlaAspTyrTyrCysProGlnSerTyrAspPheProTyrThrPheGlyGlyGlyThrLysLeuGluIleA
sn
Claims (1)
1. application of the monoclonal antibody in the kit for preparing detection parkinsonism, the heavy chain of the monoclonal antibody can
Become area successively respectively such as SEQ ID NO：1, shown in 3,5,7,9,11,13,15,17,19,21,23；The weight of the monoclonal antibody
Chain variable region is successively respectively such as SEQ ID NO：2, shown in 4,6,8,10,12,14,16,18,20,22,24.
Priority Applications (1)
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710113949.6A CN106706930B (en) | 2017-02-28 | 2017-02-28 | A kind of kit for parkinsonism detection |
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| CN106706930B true CN106706930B (en) | 2018-11-02 |
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| CN102692500B (en) * | 2011-03-21 | 2015-06-10 | 上海市肿瘤研究所 | ANGPTL4 as a marker of liver cancer metastasis by serological detection and application thereof |
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