CN104031126B - A kind of natural killer T cells activator polypeptide and application thereof - Google Patents
A kind of natural killer T cells activator polypeptide and application thereof Download PDFInfo
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- CN104031126B CN104031126B CN201410295889.0A CN201410295889A CN104031126B CN 104031126 B CN104031126 B CN 104031126B CN 201410295889 A CN201410295889 A CN 201410295889A CN 104031126 B CN104031126 B CN 104031126B
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 26
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 24
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 24
- 210000000581 natural killer T-cell Anatomy 0.000 title abstract description 23
- 239000012190 activator Substances 0.000 title description 12
- 239000003814 drug Substances 0.000 claims abstract description 6
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 10
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 9
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 239000011230 binding agent Substances 0.000 claims 1
- 239000000945 filler Substances 0.000 claims 1
- 239000000314 lubricant Substances 0.000 claims 1
- 239000003381 stabilizer Substances 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 abstract description 19
- 206010040070 Septic Shock Diseases 0.000 abstract description 7
- 230000004083 survival effect Effects 0.000 abstract description 7
- 230000004913 activation Effects 0.000 abstract description 5
- 238000012360 testing method Methods 0.000 abstract description 5
- 230000001154 acute effect Effects 0.000 abstract description 4
- 230000001629 suppression Effects 0.000 abstract description 3
- 108090000790 Enzymes Proteins 0.000 abstract description 2
- 102000004190 Enzymes Human genes 0.000 abstract description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 238000009509 drug development Methods 0.000 abstract description 2
- 238000001727 in vivo Methods 0.000 abstract description 2
- 239000002547 new drug Substances 0.000 abstract description 2
- 206010061218 Inflammation Diseases 0.000 abstract 1
- 230000004054 inflammatory process Effects 0.000 abstract 1
- 102000003390 tumor necrosis factor Human genes 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 description 19
- 102000018779 Replication Protein C Human genes 0.000 description 6
- 108010027647 Replication Protein C Proteins 0.000 description 6
- 239000002158 endotoxin Substances 0.000 description 5
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 238000011740 C57BL/6 mouse Methods 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
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- 241001465754 Metazoa Species 0.000 description 2
- 101100216185 Oryza sativa subsp. japonica AP25 gene Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 230000031700 light absorption Effects 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000002626 targeted therapy Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 102100036013 Antigen-presenting glycoprotein CD1d Human genes 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- ABLJDBFJPUWQQB-DCAQKATOSA-N Cys-Leu-Arg Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CS)N ABLJDBFJPUWQQB-DCAQKATOSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 101000716121 Homo sapiens Antigen-presenting glycoprotein CD1d Proteins 0.000 description 1
- FHIAJWBDZVHLAH-YUMQZZPRSA-N Lys-Gly-Ser Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O FHIAJWBDZVHLAH-YUMQZZPRSA-N 0.000 description 1
- DRRXXZBXDMLGFC-IHRRRGAJSA-N Lys-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCCN DRRXXZBXDMLGFC-IHRRRGAJSA-N 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- KHGNFPUMBJSZSM-UHFFFAOYSA-N Perforine Natural products COC1=C2CCC(O)C(CCC(C)(C)O)(OC)C2=NC2=C1C=CO2 KHGNFPUMBJSZSM-UHFFFAOYSA-N 0.000 description 1
- XWBJLKDCHJVKAK-KKUMJFAQSA-N Phe-Arg-Gln Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N XWBJLKDCHJVKAK-KKUMJFAQSA-N 0.000 description 1
- 208000033240 Progressive symmetric erythrokeratodermia Diseases 0.000 description 1
- FZEUTKVQGMVGHW-AVGNSLFASA-N Ser-Phe-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O FZEUTKVQGMVGHW-AVGNSLFASA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 108010062796 arginyllysine Proteins 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000003969 blast cell Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 210000000448 cultured tumor cell Anatomy 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 229930192851 perforin Natural products 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical group O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to drug world, be specifically related to have activation natural killer T cell, suppression tumor necrosis factor discharges enzyme, has the polypeptide alleviating acute inflammatory reaction to body breaks down.Its sequence be FRQSFQKVLCLRKGS be brand-new sequence, in vivo test in increase endotoxin shock mice survival rate, there is potential new drug development value.
Description
Technical field
The present invention relates to natural killer T cells activator and application thereof, be specifically related to that there is activation natural killer T cell,
The polypeptide for the treatment of acute lymphoblastic leukemia.
Background technology
Acute lymphoblastic leukemia (ALL) is a kind of Progressive symmetric erythrokeratodermia malignant disease, it is characterized by that substantial amounts of being similar to is drenched
The neocyte of bar blast cell.These cells can find in blood, bone marrow, lymph node, spleen and other organ.Acute
Lymphocytic leukemia accounts for the 80% of acute leukemia, and sickness rate peak is between 3 years old to 7 years old.ALL also can betide
Adult, accounts for the 20% of all adult leukemia.Going deep into recently as medical research, blood white to acute lymphocytic
Sick understanding and treatment have made great progress.Biological target therapy tumor is the most promising, and targeted therapy is to block to swell
Certain process that tumor occurs, reaches to treat the purpose of tumor.
Natural killer T (natural killer T cells, NKT) cell is a kind of T cell Asia with special sign
Group, had both expressed T cell surface marker, such as CD3, TCRa (mankind express Va24 V 11, and mice expresses Va14 Ja18), table again
Reach the surface marker of NK cell.NKT cell can only identify the specific sugar lipid molecule by CD1d molecule submission rather than
Polypeptide by MHC (major histocompatibility complex, MHC) submission.NKT is thin
A series of necrocytosis correlation factor can be secreted rapidly after born of the same parents' activation, such as perforin and TNF-α, strengthen its killing tumor cell
Effect；Also by activating other effector lymphocytes with killing activity, such as NK cell and CD8+ cell, play antitumor
Effect.
Therefore, activation natural killer T cell, suppression acute lymphoblastic leukemia development, is that treatment acute lymphoblastic is thin
The leukemic novel targets of born of the same parents' property.But, not yet have the treatment acute lymphoblastic of the natural killer T cells activator polypeptide of exploitation maturation
The medicine of cell leukemia.
Natural killer T cells activator polypeptide in this patent is proved in acute lymphoblastic leukemia effectively,
There is the prospect of exploitation in other tumor models.
Summary of the invention
Goal of the invention
The present invention provides brand-new sequence, this sequence natural killer T cells activator, has acute lymphoblastic leukemia
There is good curative effect.
Technical scheme
Natural killer T cells activator, it is characterised in that its sequence is FRQSFQKVLCLRKGS.
The application in preparation treatment acute lymphoblastic leukemia medicine of the natural killer T cells activator.
Beneficial effect
Utilizing solid-phase synthesis chemosynthesis natural killer T cells activator, this polypeptide has brand-new sequence, this polypeptide
Can Activated in Vitro natural killer T cells, treat acute lymphoblastic leukemia.Test increases endotoxin shock mice in vivo
Survival rate, there is potential new drug development value.
Detailed description of the invention
The present invention relates to polypeptide by gill biochemical (Shanghai) synthesis.
Embodiment 1
The chemical synthesis process of polypeptide
Polypeptide Fmoc is chemically synthesized.Synthetic reaction is carried out to N end from C end, and Rink medium (can be at Advanced
ChemTech company buys) on have free amino group, be linked in sequence aminoacid.In each step connection procedure, amino acid residue will
Activation, has HBTU, HOBt, DIEA and the Fmoc-aminoacid of free amino group on 4 times of media in activator mixture.Amino every time
After the coupled reaction of acid, all use the mixture of a pyridine/acetic acid/N-Methylimidazole. (4:1:0.5) to close and be not connected with
Free amino group, capping 10 min.After each amino acid whose coupled reaction, before next aminoacid connects, will be
Fmoc-group on medium removes, and goes Fmoc-group to use the dimethylformamide containing 20% piperidines, needs 15 minutes.Finally, when
After all amino acid residues are linked in sequence, polypeptide cuts down from medium with 98% trifluoroacetic acid, and cutting is at room temperature carried out
2 hours.
Applying above-mentioned electrochemical conditions can synthesize and obtain polypeptide, sequence is FRQSFQKVLCLRKGS, and this sequence is brand-new sequence
Row.
Embodiment 2
Natural killer T cells activator 1 is to the growth of cultured tumor cells in vitro and survival IC50.
Use MTT colorimetry.By the U937 cell of logarithmic growth, add in 96 well culture plates with 1.0 × 105, training
Supporting 24h, experimental port, positive drug control hole are separately added into Experimental agents natural killer T cells activator 1 and of variable concentrations
Positive control medicine vincristine；Blank group adds the solvent of same volume.Every hole sets five multiple holes, cultivates 48h, exists respectively
0h, 2h, 8h, 14h, 20h, 24h, 36h, the every hole of 48h add MTT, effect 4h after, add DMSO, hatch 30min, at enzyme
Absorbance A value is measured, by formula growth of tumour cell suppression ratio=(1-experimental group light absorption value/matched group at mark instrument 620nm
Light absorption value) × 100%.The IC50 calculating Experimental agents is 5.77 μMs.
Embodiment 3
Internal vigor with endotoxin shock model detection natural killer T cells activator 1
Before setting up endotoxin shock model, first we determine LPS(E. coli 0111:B4, sigma company
Buying) LD50 of white mice is every mice of 50 g, we have employed every mice of 100 g, so, matched group in an experiment
Mice can be all dead.In research work before us, find the other peptide inhibitor of Regasepin2(,
Open) C57BL/6 mice survival rate during endotoxin shock can be improved.In order to set up endogenous toxin on our white mice
Element Shock Model, we have done a positive control experiment with Regasepin2.Control group mice injects 100 g LPS, and
The mice of Regasepin2 experimental group is after injection LPS 5 minutes, and every mice injects the polypeptide of 0.7 mg again.By making
Kaplan-Meier survival curve finds that Regasepin2 can be effectively protected the mice having injected 100 g, improves existence
Rate.After successfully setting up endotoxin shock model on white mice, with this model inspection natural killer T cells activator 1
Internal vigor.Control group mice (12) injects 100 g LPS, and 1 group of mice of natural killer T cells activator (12) exists
After injection LPS 5 min, every injected in mice 0.7 mg natural killer T cells activator 1.Use Kaplan-Meier survival curve
Analyzing, natural killer T cells activator 1 can protect white mice effectively, improves the survival rate of endotoxin shock mice.
Embodiment 4
AP25 I, polypeptide II and polypeptide III are to melanin tumour b16 F10 C57BL/6 black Mus transplantation tumor
Growth inhibition test
The tumor tissue taking growth animated period is aseptically milled, and is prepared as 1 × 107Individual/ml cell suspension, with 0.1
It is subcutaneous that ml is inoculated in right side of mice armpit.Mice-transplanted tumor vernier caliper measurement transplanted tumor diameter, treats that tumor growth is to 100-
200 mm3Rear animal random packet.Use the method measuring tumor footpath, dynamically observe AP25 and animal subject is swollen
The inhibition of tumor.The pendulous frequency of diameter of tumor is every 2 days 1 time, measures every time and the most also needs to weigh Mus weight.On the left of experimental group
Armpit subcutaneous injection polypeptide, negative group is given normal saline simultaneously, is administered 14 d, its cyclophosphamide subcutaneous administration one every other day
Secondary, every 3 days subcutaneous administrations of paclitaxel group once, give twice for one day, and other respectively organizes one day by polypeptide low dosage one day administered twice group
It is administered once.After treating 14 d, sacrifice, operation strips tumor mass and weighs.The meter of gross tumor volume (tumor volume, TV)
Calculation formula is:
TV = 1/2×a×b2
Wherein a, b represent length and width respectively.
Result according to measuring calculates relative tumour volume (relative tumor volume, RTV), computing formula
For: RTV=Vt/V0.Wherein V0For (d during sub-cage administration0) measure gained gross tumor volume, VtTumor during for measuring each time
Volume.The evaluation index of anti-tumor activity is Relative tumor rate of increase T/C(%), computing formula is as follows:
TRTV: treatment group RTV；CRTV: negative control group RTV.
Test is independently repeated 3 times, and the result that test obtains calculates mean ± SD, and carries out adding up t inspection, * P <
0.05 is significant difference, and * * P < 0.01 is pole significant difference.
Table 1 polypeptide inhibitory action to melanin tumour b16 F10 C57BL/6 black Mus Growth of Tumors Transplanted
SEQUENCE LISTING
<110>Suzhou Pu Luoda bio tech ltd
<120>a kind of natural killer T cells activator polypeptide and application thereof
<130>
<160> 1
<170> PatentIn version 3.3
<210> 1
<211> 15
<212> PRT
<213>artificial sequence
<400> 1
Phe Arg Gln Ser Phe Gln Lys Val Leu Cys Leu Arg Lys Gly Ser
1 5 10 15
Claims (5)
1. a peptide species, it is characterised in that its sequence is FRQSFQKVLCLRKGS.
2. a pharmaceutical composition, it is characterised in that it comprises polypeptide as claimed in claim 1 and pharmaceutically can connect with more than one
Filler, binding agent, lubricant, disintegrating agent or the stabilizer being subject to.
3. pharmaceutical composition as claimed in claim 2, it is characterised in that described compositions is injection.
4. polypeptide as claimed in claim 1, it is characterised in that effective dose is 10mg/kg.
5. the polypeptide as claimed in claim 1 application in preparation or treatment acute lymphoblastic leukemia medicine.
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| CN201410295889.0A CN104031126B (en) | 2014-06-27 | 2014-06-27 | A kind of natural killer T cells activator polypeptide and application thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410295889.0A CN104031126B (en) | 2014-06-27 | 2014-06-27 | A kind of natural killer T cells activator polypeptide and application thereof |
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| CN104031126B true CN104031126B (en) | 2016-10-12 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101735982A (en) * | 2009-12-31 | 2010-06-16 | 浙江中赢控股集团有限公司 | Method for amplifying lymphocyte by interleukin 15 receptor and interleukin 2 complex |
| CN102460161A (en) * | 2009-04-09 | 2012-05-16 | 洛菲厄斯生物科学有限责任公司 | Method for polypeptide transfer into cells |
| CN103517917A (en) * | 2010-11-25 | 2014-01-15 | 伊姆耐特有限责任公司 | Modulation of antigen immunogenicity by addition of epitopes recognized by nkt cells |
-
2014
- 2014-06-27 CN CN201410295889.0A patent/CN104031126B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102460161A (en) * | 2009-04-09 | 2012-05-16 | 洛菲厄斯生物科学有限责任公司 | Method for polypeptide transfer into cells |
| CN101735982A (en) * | 2009-12-31 | 2010-06-16 | 浙江中赢控股集团有限公司 | Method for amplifying lymphocyte by interleukin 15 receptor and interleukin 2 complex |
| CN103517917A (en) * | 2010-11-25 | 2014-01-15 | 伊姆耐特有限责任公司 | Modulation of antigen immunogenicity by addition of epitopes recognized by nkt cells |
Non-Patent Citations (1)
| Title |
|---|
| Endogenous collagen peptide activation of CD1d-restricted NKT cells ameliorates tissue-specific inflammation in mice;Liu Yawei et.al;《J Clin Invest》;20110104;第121卷(第1期);249-264 * |
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| CN104031126A (en) | 2014-09-10 |
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