CN106589095A - Anticancer active peptide variant and application thereof - Google Patents
Anticancer active peptide variant and application thereof Download PDFInfo
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- CN106589095A CN106589095A CN201710033727.3A CN201710033727A CN106589095A CN 106589095 A CN106589095 A CN 106589095A CN 201710033727 A CN201710033727 A CN 201710033727A CN 106589095 A CN106589095 A CN 106589095A
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- polypeptide
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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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- Gastroenterology & Hepatology (AREA)
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- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
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- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides an anticancer active peptide variant. A protein variant has a better effect of inhibiting tumor cell growth relative to a wild variant. Variant proteins and their derivatives can be used for treating various 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 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 cancerous cell, and energy anticancer propagation, but weaker to normal cell and animal toxicity；Together
When may also suppress hypoxia inducible factor HIF alpha transcriptionals activity, so as to suppress tumor blood vessels to regenerate, 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 pulmonary carcinoma, hepatocarcinoma, cervical cancer
Thing has preferable application prospect.
In prior art, in order to improve the activity of polypeptide, the change of specificity is carried out for peptide sequence, so as to find work
The higher variant of property is conventional way.In order to further improve the biological activity of the polypeptide, applicant by substantial amounts of experiment,
The polypeptide obtained for this application has carried out the change of aminoacid, than original polypeptide itself there is higher suppression to live so as to obtain
The variant of property.
Detailed description of the invention
Polypeptide according to the present invention, sequence is as follows:
NB：RKGWFKAMKSIAKFIAKEKLKEHL；
(NB 1)：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 the Peptide systhesis of the present invention, free state form can be made, it is also possible to make cationic salts, such as：Tfa salt (three
Fluoroacetate), HCl salt (hydrochlorate), acetate form.
The polypeptide of the present invention, can select and one or more pharmaceutical carrier combination, multi-medicament dosage form be made, for controlling
Treat.These pharmaceutical dosage forms are covered：The dosage forms such as injection solution, tablet, cream, capsule, ointment, lotion, tongue buccal tablet are locally or systemically
Administration.Dosage preferably in the range of 10-5～10-2mg/kg body weight, with the higher concentration whole body of 0.1%-0.5% or local
Administration.For the determination of the optimal dose of concrete 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, polypeptide of the present invention is synthesized, Jing Mass Spectrometric Identifications show that purity is higher, with setting sequence
Peptide molecule structure it is identical.
Embodiment 2：Polypeptide kills cancerous cell experiment
Toxicity of the polypeptide of the present invention to 3 kinds of cell strains of Hela, CNE1 and JB6 by MTT assays.Effect is dense
Spend for 40 micromoles polypeptide of the present invention.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% erythrocyte, illustrate polypeptide of the present invention for just
Often 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 mice, shows that polypeptide toxicity of the present invention is relatively low, for cancerous cell
With stronger selectivity.
Polypeptide of the present invention have detected using the double dye methods of Annexin V- Fluorescein isothiocyanates/propidium iodide and kill cancerous cell
Mechanism, find the inducible Hela apoptosis of polypeptide of the present invention, the Hela apoptosis without drug treating are less, illustrate
Invention polypeptide kills cancerous cell by inducing cell apoptosis.
Killing result of the polypeptide of the present invention to cell strain 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 anticancer 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), matched group (normal 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 tumor 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.Complete in administration in the 10th day, it is right
It is 5 times of administration group according to the gross tumor volume of group (normal saline), and is administered as control 1 and compares 2 its tumor size of peptide and give
Medicine is similar for the matched group result of normal 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 aminoacid sequence is SEQ ID NO：Shown in 13.
2. bioactive 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 the bioactive peptide variant described in claim 1 and pharmaceutically suitable carrier.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710033727.3A CN106589095A (en) | 2017-01-17 | 2017-01-17 | Anticancer active peptide variant and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710033727.3A CN106589095A (en) | 2017-01-17 | 2017-01-17 | Anticancer active peptide variant and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106589095A true CN106589095A (en) | 2017-04-26 |
Family
ID=58584775
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710033727.3A Pending CN106589095A (en) | 2017-01-17 | 2017-01-17 | Anticancer active peptide variant and application thereof |
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| Country | Link |
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| CN (1) | CN106589095A (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 CN201710033727.3A patent/CN106589095A/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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Application publication date: 20170426 |