CN104693286A - Vascular endothelial growth factor C antagonistic polypeptide and application thereof - Google Patents
Vascular endothelial growth factor C antagonistic polypeptide and application thereof Download PDFInfo
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- CN104693286A CN104693286A CN201510157271.2A CN201510157271A CN104693286A CN 104693286 A CN104693286 A CN 104693286A CN 201510157271 A CN201510157271 A CN 201510157271A CN 104693286 A CN104693286 A CN 104693286A
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- vascular endothelial
- endothelial growth
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Abstract
The invention relates to the field of medicines, in particular to polypeptide for restraining vascular endothelial growth factors C and treating acute lymphocytic leukemia. The sequence of the polypeptide is GPREGPKPLSQCVCKHHQ which is brand new, the polypeptide can restrain the vascular endothelial growth factors C in vitro on the 1 micromole level, the survival rate of tumor-bearing mice in in-vivo tests is improved, and the polypeptide has potential new drug development value.
Description
Technical field
The present invention relates to vascular endothelial growth factor C antagonism polypeptide and application thereof, be specifically related to that there is suppression vascular endothelial growth factor C, 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 a large amount of to be similar to lymphoblastic neocyte.These cells can find in blood, marrow, lymphoglandula, spleen and other organ.Acute lymphoblastic leukemia accounts for 80% of acute leukemia, and sickness rate peak is between 3 years old to 7 years old.To the maximum threat of acute lymphoblastic leukemia patient be diffusion and transfer.How eliminating the distant metastasis of certain cancer or prevent recurrence, is indispensable integral part in cancer treatment method, is also the treatment acute lymphoblastic leukemia hot issue inquired at present.
Lymph is the colourless transparent liquid in humans and animals body, includes lymphocyte, is formed after infiltrating lymphatic vessel by tissue juice.Lymphatic vessel is the pipe that structure follows vein similar, is distributed in each portion of whole body.The different lymphocyte produced in acute lymphoblastic leukemia patient Lymphoid tissue circulates at intralymphatic, finally flows into vein, enters blood.If suppress vasculolymphatic generation, just can suppress the migration of abnormal lymphocytes, enter in blood tissues, reduce migration and the disease palindromia of leukemia cell.Therefore, the transfer of vasculolymphatic generation to leukemia cell has vital effect.
The important cytokine that VEGF-C (VEGF-C) regulates lymphatic vessel to generate, by the combination with VEGFR3, there is the complicated cascade effect of biochemical signals in VEGF-C, causes lumen to be formed and be divided into ripe lymphatic vessel.Therefore, the migration of VEGF-C and leukemia cell is closely related.Suppress VEGF-C, the combination of VEGF-C and VEGFR3 can be suppressed, suppress ripe lymphatic vessel to be formed, thus suppress the transfer of leukemia cell, effectively can reduce the symptom of disease, control advancing of disease.
At present, do not have the VEGF-C antagonism polypeptide of ripe exploitation to come out, be used for the treatment of acute lymphoblastic leukemia.
Vascular endothelial growth factor C antagonism polypeptide in this patent has proved in acute lymphoblastic leukemia effective, has the prospect developed in other tumor models.
Summary of the invention
goal of the invention
The invention provides brand-new sequence, this sequence is vascular endothelial growth factor C antagonist, has good curative effect to acute lymphoblastic leukemia.
technical scheme
vascular endothelial growth factor C antagonism polypeptide, is characterized in that its sequence is GPREGPKPLSQCVCKHHQ.
The application of vascular endothelial growth factor C antagonism polypeptide in treatment acute lymphoblastic leukemia medicine.
beneficial effect
Utilize solid-phase synthesis chemosynthesis vascular endothelial growth factor C antagonism polypeptide, this polypeptide has brand-new sequence, and this polypeptide can vitro inhibition vascular endothelial growth factor C, treatment acute lymphoblastic leukemia.The vascular endothelial growth factor C antagonism polypeptide that we find can suppress lymphatic endothelium proliferation activity simultaneously, and improves tumor-bearing mice survival rate in testing in vivo, has potential new drug development value.
Embodiment
Embodiment 1
Vascular endothelial growth factor C antagonism polypeptide is on the impact of extracorporeal blood vessel endothelial cell growth factor (ECGF) C acceptor and vascular endothelial growth factor C avidity.
By people's lymphatic endothelium of logarithmic growth, with 1.0 × 10
5add in 96 well culture plates, cultivate 24h, experimental port, positive drug control hole add Experimental agents vascular endothelial growth factor C antagonism polypeptide (the raw work synthesis in Shanghai) and the positive control medicine vincristine(VCR) of different concns respectively; Blank group adds the solvent of same volume, adds meanwhile
125the vascular endothelial growth factor C of I mark.Five multiple holes are established in every hole, cultivate 48h.Wash away supernatant liquor, use-liquid scintillation counter calculates intensity of radioactivity, and judge the bonding force of vascular endothelial growth factor C acceptor and vascular endothelial growth factor C, intensity of radioactivity intensity is stronger, and in conjunction with more, otherwise intensity of radioactivity intensity is more weak, in conjunction with fewer.Result shows, with vascular endothelial growth factor C antagonism polypeptide concentration increase, is combined with vascular endothelial growth factor C and increases gradually, illustrate and vascular endothelial growth factor C binding ability constantly reduce with the increase of drug level.
Embodiment 2
Vascular endothelial growth factor C antagonism polypeptide is to the growth of vitro culture of human lymphatic endothelium and survival IC50.
Adopt MTT colorimetry.By people's lymphatic endothelium of logarithmic growth, with 1.0 × 10
5add in 96 well culture plates, cultivate 24h, experimental port, positive drug control hole add Experimental agents vascular endothelial growth factor C antagonism polypeptide and the positive control medicine taxol of different concns respectively; Blank group adds the solvent of same volume.Five multiple holes are established in every hole, cultivate 48h, respectively 0h, 2h, 8h, 14h, 20h, 24h, 36h, the every hole of 48h adds MTT, after effect 4h, add DMSO, hatch 30min, absorbance A value is measured, by formula people lymphatic endothelium growth inhibition ratio=(1-experimental group light absorption value/control group light absorption value) × 100% at microplate reader 620nm place.The IC50 calculating Experimental agents is 1.41 μMs.
Embodiment 3
With vigor in the body of tumor model detection vascular endothelial growth factor C antagonism polypeptide.
Set up U937 tumor model, positive control medicine taxol; Blank group adds the solvent of same volume, and experimental group establishes 3 dosage: 0.75,1.5,3 mg/Kg.After 21 days, observe mouse survival quantity, calculate survival rate.Result shows, and vascular endothelial growth factor C antagonism polypeptide can protect small white mouse effectively, and improve the survival rate of tumor-bearing mice, survival rate reaches 86.9%.
SEQUENCE LISTING
Pu Luoda bio tech ltd, <110> Suzhou
<120> is about vascular endothelial growth factor C antagonism polypeptide and application thereof
<130>
<160> 1
<170> PatentIn version 3.3
<210> 1
<211> 18
<212> PRT
<213> artificial sequence
<400> 1
Gly Pro Arg Glu Gly Pro Lys Pro Leu Ser Gln Cys Val Cys Lys His
1 5 10 15
His Gln
Claims (2)
1. vascular endothelial growth factor C antagonism polypeptide, is characterized in that its sequence is GPREGPKPLSQCVCKHHQ.
2. the application of vascular endothelial growth factor C antagonism polypeptide in treatment acute lymphoblastic leukemia medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510157271.2A CN104693286A (en) | 2015-04-06 | 2015-04-06 | Vascular endothelial growth factor C antagonistic polypeptide and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510157271.2A CN104693286A (en) | 2015-04-06 | 2015-04-06 | Vascular endothelial growth factor C antagonistic polypeptide and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104693286A true CN104693286A (en) | 2015-06-10 |
Family
ID=53340873
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510157271.2A Pending CN104693286A (en) | 2015-04-06 | 2015-04-06 | Vascular endothelial growth factor C antagonistic polypeptide and application thereof |
Country Status (1)
| Country | Link |
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| CN (1) | CN104693286A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1330664A (en) * | 1998-09-30 | 2002-01-09 | 路德维格癌症研究所 | Platelet-derived growth factor C, DNA coding therefor and uses thereof |
| CN101528235A (en) * | 2006-10-27 | 2009-09-09 | 詹森药业有限公司 | Vegfr3 inhibitors |
-
2015
- 2015-04-06 CN CN201510157271.2A patent/CN104693286A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1330664A (en) * | 1998-09-30 | 2002-01-09 | 路德维格癌症研究所 | Platelet-derived growth factor C, DNA coding therefor and uses thereof |
| CN101528235A (en) * | 2006-10-27 | 2009-09-09 | 詹森药业有限公司 | Vegfr3 inhibitors |
Non-Patent Citations (1)
| Title |
|---|
| MATTHIAS RINDERKNECHT等: "Phage-Derived Fully Human Monoclonal Antibody Fragments to Human Vascular Endothelial Growth Factor-C Block Its Interaction with VEGF Receptor-2 and 3", 《PLOS ONE》 * |
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Application publication date: 20150610 |