CN105936643A - Peptide with activity on inhibiting growth of cancer cells and applications thereof - Google Patents
Peptide with activity on inhibiting growth of cancer cells and applications thereof Download PDFInfo
- Publication number
- CN105936643A CN105936643A CN201610538992.2A CN201610538992A CN105936643A CN 105936643 A CN105936643 A CN 105936643A CN 201610538992 A CN201610538992 A CN 201610538992A CN 105936643 A CN105936643 A CN 105936643A
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- China
- Prior art keywords
- peptide
- cell
- activity
- cancer cells
- growth
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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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Abstract
The invention relates to a peptide with an activity on inhibiting the growth of cancer cells and belongs to the field of biomedicine. The peptide comprises the amino sequence: NYKSRIANSDTNTSYNHI. The coding gene of the peptide comprises a nucleotide sequence: aactataaaagccgcattgcgaacagcgataccaacaccagctataaccatatt. The provided peptide can inhibit the growth of cancer cells, especially for the growth of lung cancer cells and cervical cancer cells.
Description
Technical field
The invention belongs to field of pharmaceutical biology, the present invention be more particularly to a kind of peptide with anticancer growth activity and
Application.
Background technology
During cancer occurs and treats, chemotherapy one is directly subordinate to main part.The chemotherapeutics of existing Clinical practice,
Such as cyclophosphamide, cisplatin, cytosine arabinoside, adriamycin and vincristine etc., they are primarily used to the cycle of destruction cell, R
NA, DNA and protein are all the targeting targets of this type of medicine.In recent years, As2O3 is for achieving very in leukemic treatment
Big progress, but, this medicine and other chemotherapeutics, itself there is the toxicity of oneself, no matter be a kind of chemotherapeutics list
Solely using or several chemotherapeutics R. concomitans are on clinical treatment, it is having obvious curative effects to cancer, kills cancerous cell
While, also can damage the normal cell of patient.The side effect of chemotherapeutics is most common is exactly that the bone marrow to patient 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 for not having
Cancerous tissue that peplos wraps up and aggressive tumours is had to be difficult to eradicate completely；Radiation treatment, is to utilize some tumor quick to ray
The feature of sense optionally kills cancerous cell, but poor for non-sensitive type and easy diffused cancerous cell curative effect, and is controlling
Normocellular death is will also result in during treatment；Chemotherapy, is via blood circulation by poisonous to cell, harmful medicine
Take whole body to, although also have a certain curative effect for diffused cancerous cell, but this Therapeutic Method for whole body normal cell also
Great damage can be caused, make cancer patient bear huge physiology and the torment of psychology in treatment cancer disease process.Therefore develop
The little cancer therapy drug of a kind of good effect, applied range, side effect is the common aspiration of cancer patient and medical worker.Although
Chemotherapeutics makes great progress in terms for the treatment of cancer in recent decades, but the problem that current chemotherapeutic medicine exists is the most very
Many, such as the toxicity existed, specificity is relatively low and is easily generated drug resistance, inquires into the study hotspot that novel therapies becomes current.
Biologically active peptide usually contains 2～20 amino acid residues, and its activity is along with their aminoacid of composition is different and amino
Acid puts in order difference and changes.Peptide has different physiological roles, such as antioxidation, antiproliferative, microtubulin-resisting and cell
Toxicity, these activity of peptide make them have anticancer potential, and this will contribute in treatment of cancer.Owing to peptide has the strongest
The ability penetrating tumor tissues, therefore be possible not only to arrive primary tumor target spot, it is also possible to arrive secondary tumors target
Point, these molecules mainly kill rapidly target cell, so typically not producing drug resistance by destroying the integrity of cell membrane.
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 NYKSRIANSD of aminoacid sequence
TNTSYNHI；
As a kind of preferred version, the sequence of the peptide that the present invention provides is NYKSRIANSDTNTSYNHI.
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 aactataaaagccgcattgcgaacagcgatac
caacaccagctataaccatatt。
As a kind of preferred version, the nucleotides sequence encoding above-mentioned peptide is classified as aactataaaagccgcattgcgaacagcgatacca
acaccagctataaccatatt。
The peptide of the present invention can be used for preparing the medicine with treatment entity tumor.
The peptide of the method synthesis present invention of employing chemosynthesis, the most highly developed Solid-phase peptide synthesis the most well known in the art,
Boc method can be used can also to use Fmoc method.Protected aminoacid is coupled to inertia solid phase by specific practice exactly one by one
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 the effect of anticancer growth activity, the especially growth to lung carcinoma cell or cervical cancer cell and has
There is 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 highly developed solid-phase peptide the most well known in the art
Synthetic method, both can use Boc method can also use Fmoc method.Specific practice is exactly by protected aminoacid one by one
It is coupled to inertia solid phase carrier up, then utilizes strong acid to be cleaved from carrier by peptide chain, remove side chain protected simultaneously.
Specifically, use the ABI433A type Peptide synthesizer of Perkin-Elmer company, select Fmoc/HOBt/DCC0.10
Mmol pattern, uses polypeptide solid-state reaction method to carry out bioactive peptide monomer and the synthesis of amidatioon peptide chain, and in synthesis, aminoacid used is used
Fmoc protects, and synthesis resin is HMP resin.With containing 0.6g crystalline phenol after end of synthesis, 0.4ml 3-mercaptoethanol, 0.5
Ml thioanisole, 0.5ml deionized water, peptide is cut down from resin by the cutting reagent of 12mlTFA trifluoroacetic acid.With
Reversed-phase high-performance liquid chromatography, carries out the purification of peptide on a cl 8 column.Preparing aminoacid sequence is NYKSRIANSDTNTSYNHI
Peptide.
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 using normal saline as the moon
Property comparison.Selection cell line is A549 (ATCC, U.S.A, catalog number (Cat.No.): CCL-185), Hela, human osteoblast cell's oncocyte
It is U-2OS (P53+, RB-；ATCC, U.S.A, catalog number (Cat.No.): HTB-96), plant into 1 × 10 in 24 orifice plate culture dishs5Swollen
Cell, culture fluid is 10%FBS DMEM, within second day, sucks liquid, adds embodiment 1 according to the amount of 0.005mg/ml and makes
Standby peptide or normal saline, gently sloshing fluid 3 times, at 37 DEG C, 5%CO2In hatch 180 minutes.Add containing 1%FB
Cell, to 1ml, is positioned over 37 DEG C, hatches 3-10 days in 5%CO2, observation of cell state by S DMEM culture medium.
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 | 33 | 49 | 61 |
| Hela group | 37 | 55 | 68 |
| U-2OS | 5 | 9 | 12 |
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 0.1m
It is subcutaneous that l is inoculated in axillary fossa on the right side of nude mice.With vernier caliper measurement transplanted tumor in nude mice diameter, after tumor growth to 100-200mm3
By animal random packet.Use the method measuring tumor footpath, dynamically observe the antitumous effect of tested polypeptide.The measurement of diameter of tumor
Number of times 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
Secondary；RhEndostatin group 3.0mg/kg, is administered once daily；In embodiment 1, the high, normal, basic dosage component of peptide is 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: NYKSRIANSDTNTSYNHI.
3., according to the peptide described in claim 1, the aminoacid sequence of this peptide is as follows: NYKSRIANSDTNTSYNHI.
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 aactataaaagccgcattg
cgaacagcgataccaacaccagctataaccatatt。
Nucleotide the most according to claim 4, it is characterised in that this nucleotides sequence is classified as aactataaaagccgcattgcg
aacagcgataccaacaccagctataaccatatt。
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 |
|---|---|---|---|
| CN201610538992.2A CN105936643A (en) | 2016-07-09 | 2016-07-09 | Peptide with activity on inhibiting growth of cancer cells and applications thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610538992.2A CN105936643A (en) | 2016-07-09 | 2016-07-09 | Peptide with activity on inhibiting growth of cancer cells and applications thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105936643A true CN105936643A (en) | 2016-09-14 |
Family
ID=56872330
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610538992.2A Withdrawn CN105936643A (en) | 2016-07-09 | 2016-07-09 | Peptide with activity on inhibiting growth of cancer cells and applications thereof |
Country Status (1)
| Country | Link |
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| CN (1) | CN105936643A (en) |
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 CN201610538992.2A patent/CN105936643A/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: 20160914 |