CN106699865A - Anticancer active peptide variants and application thereof - Google Patents
Anticancer active peptide variants and application thereof Download PDFInfo
- Publication number
- CN106699865A CN106699865A CN201710033742.8A CN201710033742A CN106699865A CN 106699865 A CN106699865 A CN 106699865A CN 201710033742 A CN201710033742 A CN 201710033742A CN 106699865 A CN106699865 A CN 106699865A
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- Prior art keywords
- polypeptide
- active peptide
- prt
- artificial sequence
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
- C07K14/43513—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from arachnidae
- C07K14/43518—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from arachnidae from spiders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Organic Chemistry (AREA)
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- Gastroenterology & Hepatology (AREA)
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- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Tropical Medicine & Parasitology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides anticancer active peptide variants. The protein variants have stronger effects on inhibiting tumor cell growth than the wild type. The variant proteins and derivatives thereof can be used for treating multiple tumors.
Description
Technical field
The invention belongs to biological technical field, specifically, the present invention relates to anticancer active peptide variant.
Background technology
Polypeptide cancer therapy drug is the focus of cancer drug development in recent years.In the prior art, patent application
ZL200710035478.8 isolates and purifies the anticancer active peptide for obtaining from the thick poison of Xinjiang lycosa singoriensis, is 24 peptides.This polypeptide
Energy inducing cell apoptosis kill various cancer cells, and can suppress cancer cell multiplication, but weaker to normal cell and animal toxicity；Together
When may also suppress hypoxia inducible factor HIF alpha transcriptionals activity so that suppress tumor blood vessels regeneration, effectively suppress solid tumor
Growth；The characteristics of its active anticancer has high-efficiency low-toxicity, for the medicine of the solid tumors such as exploitation treatment lung cancer, liver cancer, cervix cancer
Thing has preferable application prospect.
In the prior art, in order to improve the activity of polypeptide, specific change is carried out for polypeptide sequence, so as to find work
Property variant higher is conventional way.In order to further improve the bioactivity of the polypeptide, applicant by substantial amounts of experiment,
The polypeptide obtained for this application has carried out the change of amino acid, so as to obtain than original polypeptide there is suppression higher to live in itself
The variant of property.
Detailed description of the invention
Polypeptide of the present invention, sequence is as follows:
NB：RKGWFKAMKSIAKFIAKEKLKEHL；
(NB1)：RKGWFKAMKSTAKFIAKEKLKEHL；
(NB 2)：RKGWFKAMKSTAKFIAKEKLKEHLS；
(NB 3)：SRKGWFKAMKSTAKFIAKEKLKEHLSS；
(NB 4)：SRKGWFKAMKSTAKFIAKEKEKEHLS；
(NB 5)：SRKGWFKAMKSTAKFIAKEKSKEHLSS；
(NB 6)：SRKGSFKAMKSTAKFIAKEKSKEHLS；
(NB 7)：SRKGFKAMKSTAKFIAKEKSKEHLSS；
(NB 8)：SRKGFKAMKSTAKFIAKEKSKEHLS；
(NB 9)：RKGWAKAMKSTAKFIAKEKLKEHL；
(NB 10)：RKGWAKAMKSFAKFIAKEKLKEHL；
(NB 11)：RKGWIKAMKSFAKFIAKEKLKEHL；
(NB 12)：RKGWIKAMKSFAKFIAKEKLKEHLS；
(NB 13)：RKGWWKAMKSTAKFIAKEKLKEHLS；
(NB 14)：RKGWWKAMKSTAKFIAKEKLKEHL；
Control 1：RKGWFKAMKSWAKFIAKEKLKEHL；
Control 2：RKGWSKAMKSIAKFIAKEKLKEHL.
After Peptide systhesis of the invention, free state form can be made, it is also possible to make cationic salts, such as：Tfa salt (three
Fluoroacetate), HCl salt (hydrochloride), acetate form.
Polypeptide of the invention, can select to be combined with one or more pharmaceutical carrier, multi-medicament formulation is made, for controlling
Treat.These pharmaceutical dosage forms are covered：The formulations such as injection solution, tablet, creme, capsule, ointment, lotion, tongue lozenge are locally or systemically
Administration.Dosage preferably in the range of 10-5~10-2mg/kg body weight, with the higher concentration whole body or part of 0.1%-0.5%
Administration.Determination for the optimal dose of specific treatment is well known to those skilled in the art.
Specific embodiment
Embodiment 1：The artificial chemistry synthesis of polypeptide of the present invention
By conventional synthetic method, synthesize polypeptide of the present invention, it is higher through Mass Spectrometric Identification display purity, with setting sequence
Peptide molecule structure it is identical.
Embodiment 2：Polypeptide kills cancer cell experiment
By MTT assays, polypeptide of the present invention is to 3 kinds of toxicity of cell line of Hela, CNE1 and JB6.Effect is dense
It is 40 micromoles polypeptide of the present invention to spend.In order to further verify, detect polypeptide of the present invention for normal cell using hemolytic experiment
Toxicity, as a result show that 200 micromoles polypeptide of the present invention can only crack about 15% red blood cell, illustrate polypeptide of the present invention for just
Normal cytotoxicity is weaker.In whole animal level, we also have detected the toxicity of polypeptide of the present invention, with 200 milligrams/kg body weight skins
There is not obvious toxic reaction (in 48 hours) in lower injection mouse, shows that polypeptide toxicity of the present invention is relatively low, for cancer cell
With stronger selectivity.
Polypeptide of the present invention is have detected using the double dye methods of Annexin V- fluorescein isothiocynates/propidium iodide kill cancer cell
Mechanism, find the inducible Hela Apoptosis of polypeptide of the present invention, the Hela Apoptosis without drug-treated is less, illustrates
Invention polypeptide kills cancer cell by inducing cell apoptosis.
Killing result of the polypeptide of the present invention to cell line in 3
The polypeptide of the present invention of embodiment 3 suppresses the growth of nude mice lotus knurl
Above-mentioned experiment shows that there is polypeptide of the present invention stronger suppression cancer cell to act on, but still it needs to be determined that polypeptide of the present invention
Whether there is the effect in body solid tumor resisting, conducted a research using nude mice lotus knurl model.Experimental result shows that polypeptide of the present invention can be bright
It is aobvious to suppress implanted solid tumor growth.Before administration (0 day), control group (physiological saline) is similar with the solid tumor size size of administration group,
And within the time of pharmaceutical intervention, the gross tumor volume of saline control group quickly increases, show its tumour continued propagation, and give
The gross tumor volume of NB and NB1-14 does not have significant change in medicine group, illustrates that tumour growth is suppressed.Completed in administration in the 10th day, it is right
Gross tumor volume according to group (physiological saline) is 5 times of administration group, and is administered as control 1 and compares 2 its tumor size of peptide and give
Medicine is similar for the control group result of physiological saline, and tumor size is suitable.The above results show that polypeptide of the present invention can effectively suppress
Tumour growth.
Sequence table
<110>Li Luqing
<120>A kind of anticancer active peptide variant variant and its application
<160> 17
<210> 1
<211> 24
<212> PRT
<213>Artificial sequence
<400> 1
RKGWFKAMKSIAKFIAKEKLKEHL；
<210> 2
<211> 24
<212> PRT
<213>Artificial sequence
<400> 2
RKGWFKAMKSTAKFIAKEKLKEHL；
<210> 3
<211> 25
<212> PRT
<213>Artificial sequence
<400> 3
RKGWFKAMKSTAKFIAKEKLKEHLS
<210> 4
<211> 27
<212> PRT
<213>Artificial sequence
<400> 4
SRKGWFKAMKSTAKFIAKEKLKEHLSS；
<210> 5
<211> 26
<212> PRT
<213>Artificial sequence
<400> 5
SRKGWFKAMKSTAKFIAKEKEKEHLS；
<210> 6
<211> 27
<212> PRT
<213>Artificial sequence
<400> 6
SRKGWFKAMKSTAKFIAKEKSKEHLSS；
<210> 7
<211> 26
<212> PRT
<213>Artificial sequence
<400> 7
SRKGSFKAMKSTAKFIAKEKSKEHLS；
<210> 8
<211> 27
<212> PRT
<213>Artificial sequence
<400> 8
SRKGFKAMKSTAKFIAKEKSKEHLSS；
<210> 9
<211> 26
<212> PRT
<213>Artificial sequence
<400> 9
SRKGFKAMKSTAKFIAKEKSKEHLS；
<210> 10
<211> 24
<212> PRT
<213>Artificial sequence
<400> 10
RKGWAKAMKSTAKFIAKEKLKEHL；
<210> 11
<211> 24
<212> PRT
<213>Artificial sequence
<400> 11
RKGWAKAMKSFAKFIAKEKLKEHL；
<210> 12
<211> 24
<212> PRT
<213>Artificial sequence
<400> 12
RKGWIKAMKSFAKFIAKEKLKEHL；
<210> 13
<211> 25
<212> PRT
<213>Artificial sequence
<400> 13
RKGWIKAMKSFAKFIAKEKLKEHLS；
<210> 14
<211> 25
<212> PRT
<213>Artificial sequence
<400> 14
RKGWWKAMKSTAKFIAKEKLKEHLS；
<210> 15
<211> 24
<212> PRT
<213>Artificial sequence
<400> 15
RKGWWKAMKSTAKFIAKEKLKEHL；
<210> 16
<211> 24
<212> PRT
<213>Artificial sequence
<400> 16
RKGWFKAMKSWAKFIAKEKLKEHL；
<210> 17
<211> 24
<212> PRT
<213>Artificial sequence
<400> 17
RKGWSKAMKSIAKFIAKEKLKEHL
Claims (3)
1. a kind of anticancer active peptide, its amino acid sequence is SEQ ID NO：Shown in 8.
2. active peptide variant as claimed in claim 1 is preparing the purposes in suppressing tumour medicine.
3. a kind of anti-tumor medicinal preparation, it contains active peptide variant described in claim 1 and pharmaceutically suitable carrier.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710033742.8A CN106699865A (en) | 2017-01-17 | 2017-01-17 | Anticancer active peptide variants and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710033742.8A CN106699865A (en) | 2017-01-17 | 2017-01-17 | Anticancer active peptide variants and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106699865A true CN106699865A (en) | 2017-05-24 |
Family
ID=58907029
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710033742.8A Pending CN106699865A (en) | 2017-01-17 | 2017-01-17 | Anticancer active peptide variants and application thereof |
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| CN (1) | CN106699865A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1159918A (en) * | 1996-11-04 | 1997-09-24 | 内蒙古医学院 | Method for preparing anticancer bioactive peptide preparation |
| CN101168563A (en) * | 2007-07-31 | 2008-04-30 | 厦门北大之路生物工程有限公司 | Anticancer active peptide |
| CN104109193A (en) * | 2014-06-30 | 2014-10-22 | 陈秀定 | Variants of peptide with antitumor activity and application thereof |
| CN104592356A (en) * | 2014-06-27 | 2015-05-06 | 马海龙 | Anti-tumor peptide variant NC5 and application thereof |
-
2017
- 2017-01-17 CN CN201710033742.8A patent/CN106699865A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1159918A (en) * | 1996-11-04 | 1997-09-24 | 内蒙古医学院 | Method for preparing anticancer bioactive peptide preparation |
| CN101168563A (en) * | 2007-07-31 | 2008-04-30 | 厦门北大之路生物工程有限公司 | Anticancer active peptide |
| CN104592356A (en) * | 2014-06-27 | 2015-05-06 | 马海龙 | Anti-tumor peptide variant NC5 and application thereof |
| CN104109193A (en) * | 2014-06-30 | 2014-10-22 | 陈秀定 | Variants of peptide with antitumor activity and application thereof |
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| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170524 |