CN106146620A - There is peptide and the application thereof of anticancer growth activity - Google Patents
There is peptide and the application thereof of anticancer growth activity Download PDFInfo
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- CN106146620A CN106146620A CN201610538971.0A CN201610538971A CN106146620A CN 106146620 A CN106146620 A CN 106146620A CN 201610538971 A CN201610538971 A CN 201610538971A CN 106146620 A CN106146620 A CN 106146620A
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- peptide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
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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)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to a kind of peptide with anticancer growth activity, belong to field of pharmaceutical biology, described peptide comprises following aminoacid sequence: FYQVMGQYTYMLFLPCE, and its encoding gene comprises nucleotide sequence ttttatcaggtgatgggccagtatacctatatgctgtttctgccgtgcgaa.The peptide of the present invention has the effect of anticancer growth activity, the especially growth to lung carcinoma cell or cervical cancer cell and has inhibitory activity.
Description
Technical field
The invention belongs to field of pharmaceutical biology, the present invention has been more particularly to a kind of have anticancer growth activity
Peptide and application thereof.
Background technology
During cancer occurs and treats, chemotherapy one is directly subordinate to main part.The change of existing Clinical practice
Treating medicine, such as cyclophosphamide, cisplatin, cytosine arabinoside, adriamycin and vincristine etc., they are primarily used to destroy the week of cell
Phase, R NA, DNA and protein are all the targeting targets of this type of medicine.In recent years, As2O3 is in leukemic treatment
Make great progress, but, this medicine and other chemotherapeutics, itself there is the toxicity of oneself, no matter be oneization
Treatment medicine is used alone or several chemotherapeutics R. concomitans are on clinical treatment, and it is having obvious curative effects to cancer, kills
While killing cancerous cell, also can damage the normal cell of patient.The side effect of chemotherapeutics is most common to patient
Bone marrow produces extremely suppression, causes the considerable distress of patient, even causes death.
Treatment for cancer at present mainly has following several: operative treatment, preferable for benign tumor curative effect, but right
It is difficult to eradicate completely in the cancerous tissue not having peplos to wrap up and aggressive tumours；Radiation treatment, is to utilize some tumor pair
The feature of radiation-sensitive optionally kills cancerous cell, but poor for non-sensitive type and easy diffused cancerous cell curative effect,
And will also result in Normocellular death over the course for the treatment of；Chemotherapy, be by poisonous to cell, harmful medicine via
Blood circulation takes whole body to, although also have certain curative effect for diffused cancerous cell, but this Therapeutic Method is for whole body
Normal cell will also result in great damage, makes cancer patient bear huge physiology and the folding of psychology in treatment cancer disease process
Mill.Therefore the cancer therapy drug developing a kind of good effect, applied range, side effect little is cancer patient and medical worker
Common aspiration.Although chemotherapeutics makes great progress in terms for the treatment of cancer in recent decades, but current chemotherapeutic medicine
The problem existed is still a lot, and such as the toxicity existed, specificity is relatively low and is easily generated drug resistance, and discussion novel therapies becomes works as
Front study hotspot.
Biologically active peptide usually contains 2～20 amino acid residues, its activity along with their aminoacid of composition different with
And sequence of amino acid is different and change.Peptide has different physiological roles, such as antioxidation, antiproliferative, microtubulin-resisting
And cytotoxicity, these activity of peptide make them have anticancer potential, and this will contribute in treatment of cancer.Owing to peptide has
There is the strongest ability penetrating tumor tissues, be therefore possible not only to arrive the target spot of primary tumor, it is also possible to arrive Secondary cases
The target spot of tumor, these molecules mainly kill rapidly target cell, so typically not producing by destroying the integrity of cell membrane
Raw drug resistance.
Summary of the invention
The present invention seeks to for the problems referred to above, it is provided that a kind of peptide with anticancer growth activity and application thereof.
Object of the present invention is to provide the peptide of a kind of anticancer growth, it comprises the peptide of aminoacid sequence
FYQVMGQYTY MLFLPCE；
As a kind of preferred version, the sequence of the peptide that the present invention provides is FYQVMGQYTYMLFLPCE.
Present invention also offers the nucleotide sequence encoding this small peptide.
As a kind of preferred version, the nucleotide sequence encoding above-mentioned peptide comprises
ttttatcaggtgatgggccagtatacctatatgctgtttctgccgtgcgaa。
As a kind of preferred version, the nucleotides sequence encoding above-mentioned peptide is classified as
ttttatcaggtgatgggccagtatacctatatgctgtttctgccgtgcgaa。
The peptide of the present invention can be used for preparing the medicine with treatment entity tumor.
Using the peptide of the method synthesis present invention of chemosynthesis, the most highly developed solid-phase peptide the most well known in the art is closed
One-tenth method, can use Boc method can also use Fmoc method.Protected aminoacid is coupled to by specific practice exactly one by one
Inertia solid phase carrier up, then utilizes strong acid to be cleaved from carrier by peptide chain, removes side chain protected simultaneously.
The peptide of the present invention has an effect of anticancer growth activity, especially to lung carcinoma cell or cervical cancer cell
Growth has inhibitory activity.
Detailed description of the invention
Embodiment 1
The synthesis of peptide of the present invention:
The present invention uses the peptide described in method preparation of chemosynthesis, the most well known in the art the most highly developed
Solid-phase peptide synthesis, both can use Boc method can also use Fmoc method.Specific practice is exactly by protected amino
Acid is coupled to inertia solid phase carrier up one by one, then utilizes strong acid to be cleaved from carrier by peptide chain, removes side chain simultaneously
Protection.
Specifically, use the ABI433A type Peptide synthesizer of Perkin-Elmer company, select Fmoc/HOBt/
DCC0.10mmol pattern, uses polypeptide solid-state reaction method to carry out bioactive peptide monomer and the synthesis of amidatioon peptide chain, used in synthesis
Aminoacid Fmoc protects, and synthesis resin is HMP resin.With containing 0.70g crystalline phenol, 0.30ml dimercapto second after end of synthesis
Alcohol, 0.35ml thioanisole, 0.5ml deionized water, under peptide is cut from resin by the cutting reagent of 10mlTFA trifluoroacetic acid
Come.With reversed-phase high-performance liquid chromatography, carry out the purification of peptide on a cl 8 column.Preparing aminoacid sequence is
The peptide of FYQVMGQYTYMLFLPC E.
Embodiment 2
The test of anticancer:
The purpose of the present embodiment is the effect testing described peptide in a series of tumor cells, and experiment will be with normal saline
As negative control.Selection cell line is A549 (ATCC, U.S.A, catalog number (Cat.No.): CCL-185), and Hela, human osteoblast cell's tumor is thin
Born of the same parents system U-2OS (P53+, RB-；ATCC, U.S.A, catalog number (Cat.No.): HTB-96), plant into 1 × 10 in 24 orifice plate culture dishs5Swollen thin
Born of the same parents, culture fluid is 10%FBS DMEM, within second day, sucks liquid, adds the peptide of embodiment 1 preparation according to the amount of 0.005mg/ml
Or normal saline, sloshing fluid 3 times gently, at 37 DEG C, 5%CO2In hatch 180 minutes.Add and cultivate containing 1%FB S DMEM
Cell, to 1ml, is positioned over 37 DEG C, hatches 3-10 days in 5%CO2, observation of cell state by base.
Experimental result is as shown in table 1 below:
The experimental result of table 1 peptide suppression growth of tumour cell
| Group | 3 days suppression ratio (%) | 5 days suppression ratio (%) | 10 days suppression ratio (%) |
| A549 group | 39 | 56 | 66 |
| Hela group | 43 | 59 | 64 |
| U-2OS | 10 | 14 | 19 |
The peptide of the present invention is more sensitive to A549 and Hela cell as can be seen from the above table.
Embodiment 3
The experiment of suppression mouse interior tumor:
Take the logarithm the HepG2 cell strain of trophophase, be aseptically prepared as 1 × 107/ ml cell suspension, with
It is subcutaneous that 0.1m l is inoculated in axillary fossa on the right side of nude mice.With vernier caliper measurement transplanted tumor in nude mice diameter, treat that tumor growth is to 100-
By animal random packet after 200mm3.Use the method measuring tumor footpath, dynamically observe the antitumous effect of tested polypeptide.Tumor is straight
The pendulous frequency in footpath is to survey 1 time for every 1 day.Administering mode all uses tail vein injection.Negative control group injection normal saline,
Every day 1 time；RhEndostatin group 3.0mg/kg, is administered once daily；In embodiment 1 the high, normal, basic dosage component of peptide not with 10mg/kg,
5mg/kg, 1mg/kg are dosage, are administered once daily.After off-test, sacrifice, operation strips tumor mass and weighs.Its knot
Fruit see table shown in 2:
The experimental result (often group nude mice quantity n=5) of table 2 peptide suppression mouse interior tumor
Claims (8)
1. a peptide, it is characterised in that: described peptide has anticancer growth activity, especially suppression lung carcinoma cell or uterus
The activity of neck cancer cell.
2., according to the peptide described in claim 1, this peptide comprises following aminoacid sequence: FYQVMGQYTYMLFLPCE.
3., according to the peptide described in claim 1, the aminoacid sequence of this peptide is as follows: FYQVMGQYTYMLFLPCE.
4. the nucleotide encoding peptide according to claim 1.
Nucleotide the most according to claim 4, it is characterised in that this nucleotide sequence comprises
ttttatcaggtgatgggccagtatacctatatgctgtttctgccgtgcgaa。
Nucleotide the most according to claim 4, it is characterised in that this nucleotides sequence is classified as
ttttatcaggtgatgggccagtatacctatatgctgtttctgccgtgcgaa。
7. the application of the described peptide in claim 1-3, it is characterised in that this application is the activity of suppression growth of tumour cell.
8., according to the application described in claim 7, described tumor cell refers to lung carcinoma cell or cervical cancer cell.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610538971.0A CN106146620A (en) | 2016-07-09 | 2016-07-09 | There is peptide and the application thereof of anticancer growth activity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610538971.0A CN106146620A (en) | 2016-07-09 | 2016-07-09 | There is peptide and the application thereof of anticancer growth activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106146620A true CN106146620A (en) | 2016-11-23 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610538971.0A Withdrawn CN106146620A (en) | 2016-07-09 | 2016-07-09 | There is peptide and the application thereof of anticancer growth activity |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1753909A (en) * | 2002-03-19 | 2006-03-29 | 株式会社康福来 | Peptides and pharmaceutical compositions comprising said peptides and medical composition for treating cancer |
| CN102488890A (en) * | 2011-12-27 | 2012-06-13 | 中国药科大学 | Application of integrin blocker polypeptide AP25 in preparation of medicines for treating tumor |
| CN102971336A (en) * | 2010-05-27 | 2013-03-13 | 埃斯泰·苏济·阿莱特·费卢 | Peptide for use as a medicament, in particular for the treatment of cancer |
| CN104271590A (en) * | 2012-01-24 | 2015-01-07 | Inter-K私人有限公司 | Peptide agents for cancer therapy |
-
2016
- 2016-07-09 CN CN201610538971.0A patent/CN106146620A/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1753909A (en) * | 2002-03-19 | 2006-03-29 | 株式会社康福来 | Peptides and pharmaceutical compositions comprising said peptides and medical composition for treating cancer |
| CN102971336A (en) * | 2010-05-27 | 2013-03-13 | 埃斯泰·苏济·阿莱特·费卢 | Peptide for use as a medicament, in particular for the treatment of cancer |
| CN102488890A (en) * | 2011-12-27 | 2012-06-13 | 中国药科大学 | Application of integrin blocker polypeptide AP25 in preparation of medicines for treating tumor |
| CN104271590A (en) * | 2012-01-24 | 2015-01-07 | Inter-K私人有限公司 | Peptide agents for cancer therapy |
Non-Patent Citations (5)
| Title |
|---|
| SERGEY CHERNYSH 等: "Antiviral and antitumor peptides from insects", 《PNAS》 * |
| 冯倩 等: "利用噬菌体随机肽库筛选人肝再生增强因子特异结合肽及其抗肝癌作用的研究", 《第三军医大学学报》 * |
| 刘丽华 等: "重组血管基膜衍生多功能肽抑制人肝癌HepG2裸鼠移植瘤生长和血管生成", 《湖南师范大学学报(医学版)》 * |
| 夏金堂 等: "VEGF—C反义多肽对人肝癌细胞HepG2增殖及侵袭的抑制效应", 《国际肿瘤学杂志》 * |
| 张兵 等: "特异性CTL治疗人肝癌裸鼠皮下移植瘤", 《西部医学》 * |
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Application publication date: 20161123 |