CN103755788B - Immunosuppression sphaeroprotein K light chain gene enhanser protein polypeptide and application thereof - Google Patents
Immunosuppression sphaeroprotein K light chain gene enhanser protein polypeptide and application thereof Download PDFInfo
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- CN103755788B CN103755788B CN201310748607.3A CN201310748607A CN103755788B CN 103755788 B CN103755788 B CN 103755788B CN 201310748607 A CN201310748607 A CN 201310748607A CN 103755788 B CN103755788 B CN 103755788B
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 17
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 12
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 12
- 108090000623 proteins and genes Proteins 0.000 title abstract description 17
- 102000004169 proteins and genes Human genes 0.000 title description 4
- 206010062016 Immunosuppression Diseases 0.000 title description 3
- 230000001506 immunosuppresive effect Effects 0.000 title description 3
- 206010040070 Septic Shock Diseases 0.000 claims abstract description 8
- 230000004083 survival effect Effects 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims description 2
- 108090000328 Arrestin Proteins 0.000 abstract description 10
- 102000003916 Arrestin Human genes 0.000 abstract description 9
- 206010061218 Inflammation Diseases 0.000 abstract description 7
- 230000004054 inflammatory process Effects 0.000 abstract description 7
- 230000036039 immunity Effects 0.000 abstract description 3
- 230000001154 acute effect Effects 0.000 abstract description 2
- 238000009509 drug development Methods 0.000 abstract 1
- 238000001727 in vivo Methods 0.000 abstract 1
- 239000002547 new drug Substances 0.000 abstract 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 12
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 108060003951 Immunoglobulin Proteins 0.000 description 7
- 206010040047 Sepsis Diseases 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- 102000018358 immunoglobulin Human genes 0.000 description 7
- 102000003945 NF-kappa B Human genes 0.000 description 6
- 108010057466 NF-kappa B Proteins 0.000 description 6
- 239000002158 endotoxin Substances 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 3
- 102000018594 Tumour necrosis factor Human genes 0.000 description 3
- 108050007852 Tumour necrosis factor Proteins 0.000 description 3
- 102000008102 Ankyrins Human genes 0.000 description 2
- 108010049777 Ankyrins Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 208000038016 acute inflammation Diseases 0.000 description 2
- 230000006022 acute inflammation Effects 0.000 description 2
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- 239000007924 injection Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 241000219357 Cactaceae Species 0.000 description 1
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- 241000588724 Escherichia coli Species 0.000 description 1
- ZSWGJYOZWBHROQ-RWRJDSDZSA-N Glu-Ile-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZSWGJYOZWBHROQ-RWRJDSDZSA-N 0.000 description 1
- 101000961071 Homo sapiens NF-kappa-B inhibitor alpha Proteins 0.000 description 1
- 108700040486 I kappa B beta Proteins 0.000 description 1
- AWOMRHGUWFBDNU-ZPFDUUQYSA-N Met-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCSC)N AWOMRHGUWFBDNU-ZPFDUUQYSA-N 0.000 description 1
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- QGOZJLYCGRYYRW-KKUMJFAQSA-N Pro-Glu-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O QGOZJLYCGRYYRW-KKUMJFAQSA-N 0.000 description 1
- 101150064657 SWI6 gene Proteins 0.000 description 1
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- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to pharmaceutical field, be specifically related to that there is Promote immunity sphaeroprotein K light chain gene enhanser arrestin, have and alleviate the polypeptide of acute inflammatory reaction to body breaks down.Its sequence is MQISEPEITPEY is brand-new sequence, and they increase the survival rate of endotoxin shock mouse in can testing in vivo, have potential new drug development value.
Description
Technical field
The present invention relates to immunoglobulin (Ig) K light chain gene enhanser arrestin polypeptide and application thereof, be specifically related to that there is Promote immunity sphaeroprotein K light chain gene enhanser arrestin, have and alleviate the polypeptide of acute inflammatory reaction to body breaks down.
Background technology
Pyemia (sepsis) is a serious medical problem always.Early stage pyemia can be in progress as severe pyemia and pyemia shock without timely and effective treatment, and both mortality ratio are respectively 20% ~ 30% and 40% ~ 70%.Medical circle is studying effective treatment means always, as early stage symptomatic treatment, activated protein c, corticosteroid therapy etc.Going deep in recent years along with medical research, has made great progress the understanding of pyemia and treatment.Wherein, immunoglobulin (Ig) K light chain gene enhanser arrestin (IKB-α) plays key player in endotoxin shock.
IKB protein family member has the Cactus etc. of IKB α (MAD-3, pp40), IKB β, IKB γ/p105, IKB δ/p100, IKB ε, Bcl-3 and Drosophila.Its family structure feature all has multiple about 33 amino acid whose tumor-necrosis factor glycoproteinss, is called Queensland SWI6/ ankyrin repeat, and main participation interacts with the RHD of Rel albumen.IKB albumen mainly contains following three parts and forms: 1. relevant with proteolytic degradation N-end region; 2. mainly can participate in interacting with the RHD of Rel albumen with the interactional inner area of NF-κ B (containing ankyrin repeat ANK in district) (family's apokoinou construction); 3. be called the C-petiolarea of PEST, main " imprison " NF-κ B that participates in is in cytoplasm.IKBs family participates in two signal paths: NF-κ B and Toll-like Receptor signal path.The activation of NF-κ B must pass through two steps: 1. IKB dissociates and degrades from NF-κ B complex body, exposes the nuclear localization sequence of NF-κ B; 2. there is core transposition in NF-κ B, and be combined with special κ B sequence.
Therefore, IKB is by these two paths of mediation, thus the generation of regulation and control Preinflammtory cytokine, cell surface receptor, transcription factor, adhesion molecule etc.The effect of final generation anti-inflammatory.Thus the major target class that treatment neutrophil leucocyte is main inflammatory reaction is become.However, the immunoglobulin (Ig) K light chain gene enhanser arrestin peptide inhibitor of unripe exploitation comes out, and is used for the treatment of pyemia.
Summary of the invention
goal of the invention
The invention provides brand-new sequence, this sequence is immunoglobulin (Ig) K light chain gene enhanser arrestin polypeptide, has good curative effect to acute inflammation.
technical scheme
immunoglobulin (Ig) K light chain gene enhanser arrestin polypeptide, is characterized in that its sequence is MQISEPEITPEY.
The application of immunoglobulin (Ig) K light chain gene enhanser arrestin polypeptide in treatment acute inflammation medicine.
beneficial effect
Utilize solid-phase synthesis chemosynthesis immunoglobulin (Ig) K light chain gene enhanser arrestin polypeptide, this polypeptide has brand-new sequence, and this polypeptide can external Promote immunity sphaeroprotein K light chain gene enhanser arrestin vigor.The survival rate of mouse is successfully added in endotoxin shock model experiment.Mononuclear macrophage expressing tumor necrosin release enzyme, this enzyme can cut and release tumor necrosis factor, and tumour necrosis factor is the core cytokine of inflammatory reaction, has the effect that exacerbate inflammation is reacted.The peptide inhibitor that we find can the enzyme activity of Tumor suppression necrosin release enzyme, thus alleviates inflammatory reaction, protection body the destruction reduced inflammation.
The present invention relates to polypeptide to be synthesized by the biochemical (Shanghai) Co., Ltd. of gill.
Embodiment
Embodiment 1
The external target spot enzyme of peptide inhibitor: the IC50 value of tumour necrosis factor release enzyme (being all purchased from sigma company).
The vigor of tumour necrosis factor release enzyme produces substrate Mca-Pro-Leu-Ala-Gln-Ala-Val-Dpa-Arg-Ser-Ser-Ser-Arg-NH by cutting fluorescence and detects (excitation wavelength=320 nm, emission wavelength=405 nm).Reaction is carried out in 100 μ l reaction systems under 37 ° of C.Reaction adds 4 μ l Transin-1s storage liquid (1 ng/ μ l) substrates in reaction system final concentration when starting is 10 μMs.The IC50 value recorded is 39.91 μm of ol.
Embodiment 2
With vigor in the body of endotoxin shock model detection polypeptide
Before setting up endotoxin shock model, first we determine LPS(E. coli 0111:B4) LD50 of small white mouse is 50 μ g every mouse, we have employed 100 μ g every mouse in an experiment, and like this, the mouse of control group can be all dead.A positive control experiment has been done with Regasepin2.Control group mice injects 100 μ g LPS, and the mouse of Regasepin2 experimental group is after injection LPS 5 minutes, and every mouse injects the polypeptide of 0.7 mg again.Finding that Regasepin2 effectively can protect the mouse of having injected 100 μ g by making Kaplan-Meier survival curve, improve survival rate.After successfully setting up endotoxin shock model on small white mouse, with vigor in the body of this model inspection MQISEPEITPEY.Control group mice (12) injects 100 μ g LPS, and peptide inhibitor group mouse (12) is after injection LPS 5 min, every injected in mice 0.7 mg peptide inhibitor.Analyze with Kaplan-Meier survival curve, polypeptide MQISEPEITPEY can protect small white mouse effectively, improves the survival rate of endotoxin shock mouse.
SEQUENCE LISTING
<110> timely snow, sieve
<120> Immunosuppression sphaeroprotein K light chain gene enhanser protein polypeptide and application thereof
<130>
<160> 1
<170> PatentIn version 3.3
<210> 1
<211> 12
<212> PRT
<213> artificial sequence
<400> 1
Met Gln Ile Ser Glu Pro Glu Ile Thr Pro Glu Tyr
1 5 10
Claims (2)
1. a peptide species, is characterized in that its sequence is MQISEPEITPEY.
2. polypeptide as claimed in claim 1 improves the application in the survival rate medicine of the mouse of endotoxin shock in preparation.
Priority Applications (1)
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| CN201310748607.3A CN103755788B (en) | 2013-12-31 | 2013-12-31 | Immunosuppression sphaeroprotein K light chain gene enhanser protein polypeptide and application thereof |
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| CN201310748607.3A CN103755788B (en) | 2013-12-31 | 2013-12-31 | Immunosuppression sphaeroprotein K light chain gene enhanser protein polypeptide and application thereof |
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| Publication Number | Publication Date |
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| CN103755788A CN103755788A (en) | 2014-04-30 |
| CN103755788B true CN103755788B (en) | 2015-10-14 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101132811A (en) * | 2004-10-22 | 2008-02-27 | 米迪缪尼股份有限公司 | High affinity antibodies against HMGB1 and methods of use thereof |
| CN101402676A (en) * | 2008-11-12 | 2009-04-08 | 西南大学 | Polyglycols modified disinfection/neutralization endotoxin polypeptide, preparation and uses thereof |
| CN103304634A (en) * | 2013-05-30 | 2013-09-18 | 苏州普罗达生物科技有限公司 | Matrix metalloproteinase-2 polypeptide inhibitor and application |
-
2013
- 2013-12-31 CN CN201310748607.3A patent/CN103755788B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101132811A (en) * | 2004-10-22 | 2008-02-27 | 米迪缪尼股份有限公司 | High affinity antibodies against HMGB1 and methods of use thereof |
| CN101402676A (en) * | 2008-11-12 | 2009-04-08 | 西南大学 | Polyglycols modified disinfection/neutralization endotoxin polypeptide, preparation and uses thereof |
| CN103304634A (en) * | 2013-05-30 | 2013-09-18 | 苏州普罗达生物科技有限公司 | Matrix metalloproteinase-2 polypeptide inhibitor and application |
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| CN103755788A (en) | 2014-04-30 |
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Owner name: GU XIANGMAO Free format text: FORMER OWNER: LUO RUIXUE Effective date: 20150901 |
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Effective date of registration: 20150901 Address after: 266000 Licang, Qingdao, No. nine East water road, No. 320, No. Applicant after: Gu Xiangmao Address before: 639 No. 211198 Jiangsu province Nanjing city Jiangning District University City longmian Road Applicant before: Luo Ruixue |
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Inventor after: Li Xiaoxiang Inventor before: Luo Ruixue |
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Effective date of registration: 20160323 Address after: 100037, 58, Fu Cheng Road, Beijing, 6 floor, Room 608, Haidian District Patentee after: Niu Saier bio tech ltd, Beijing Address before: 266000 Licang, Qingdao, No. nine East water road, No. 320, No. Patentee before: Gu Xiangmao |
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Effective date of registration: 20170720 Address after: Fuchuan Yao Autonomous County of Fuyang New Town Road 542700 the Guangxi Zhuang Autonomous Region Hezhou City No. 34 Patentee after: Yuan Jialing Address before: 100037, 58, Fu Cheng Road, Beijing, 6 floor, Room 608, Haidian District Patentee before: Niu Saier bio tech ltd, Beijing |
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Inventor after: Ling Zisong Inventor before: Li Xiaoxiang |
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Effective date of registration: 20170920 Address after: 510000 A02 office, No. 38, Lu Yuan Road, Yuexiu District, Guangdong, Guangzhou two, China. Two Patentee after: Guangzhou Qixin Biological Technology Co. Ltd. Address before: Fuchuan Yao Autonomous County of Fuyang New Town Road 542700 the Guangxi Zhuang Autonomous Region Hezhou City No. 34 Patentee before: Yuan Jialing |
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Granted publication date: 20151014 Termination date: 20171231 |