CN106831945B - Polypeptide and application thereof in treating acute kidney injury - Google Patents
Polypeptide and application thereof in treating acute kidney injury Download PDFInfo
- Publication number
- CN106831945B CN106831945B CN201710223327.9A CN201710223327A CN106831945B CN 106831945 B CN106831945 B CN 106831945B CN 201710223327 A CN201710223327 A CN 201710223327A CN 106831945 B CN106831945 B CN 106831945B
- Authority
- CN
- China
- Prior art keywords
- peptide
- sequence
- injury
- polypeptide
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- 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
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Life Sciences & Earth Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention constructs 11 peptide with carboxyl at the C terminal, and 32 peptide and 22 peptide containing 11 peptide amino acid sequence. The 32 peptide and the 11 peptide can remarkably inhibit DNA damage reaction, apoptosis and inflammation of Adriamycin (ADR) treated or hypoxia reperfusion (H/R) renal tubular cells, wherein the 11 peptide is the best effect. In a C57 mouse model, the 32 peptide and the 11 peptide can obviously relieve the ischemia-reperfusion injury (I/R injury for short) of the kidney of a mouse; the 22 peptide also alleviated the damage to some extent. The 11 peptide, the 32 peptide and the 22 peptide can be used for preparing a therapeutic drug for treating acute kidney injury.
Description
Technical Field
The invention belongs to the field of biological pharmacy, and particularly relates to a polypeptide and application thereof in treating acute kidney injury.
Background
Acute kidney injury is a disease with a high global mortality rate, and ischemia or toxic injury of renal tubular cells causes a sharp decrease in renal function. Acute kidney injury is one of the major causes of end-stage renal disease. Acute kidney injury occurs in 1.33 billion people per year and approximately 170 deaths occur each year.
Ischemia reperfusion injury of the kidney is the leading cause of acute kidney injury and has a high global mortality rate. The pathological processes of renal ischemia reperfusion include the occurrence of inflammation and the occurrence of apoptosis. Effective inhibition of pro-inflammatory cytokines and apoptosis can protect against acute renal ischemia reperfusion injury. The existing medical technology has no effective means for treatment, and the survival time of a nephropathy patient is prolonged by renal replacement therapy, so that the search for drugs for relieving renal ischemia-reperfusion injury is urgent.
Disclosure of Invention
In view of the above defects or needs for improvement in the prior art, the present invention provides a polypeptide and its use, which aims to provide 11 peptides with carboxyl at the C-terminal and 22 peptides and 32 peptides comprising the amino acid sequence of 11 peptides, and to be used for acute renal injury repair, wherein the 11 peptides and 32 peptides of the present invention have significant protective effects on ischemia-reperfusion injury of the kidney; the 22 peptide has a protective effect on the ischemia reperfusion injury of the kidney to a certain extent, thereby solving the technical problem that the prior art lacks an effective treatment means for acute kidney injury.
To achieve the above object, according to one aspect of the present invention, there is provided a polypeptide whose amino acid sequence includes a first sequence:
(1) consisting of SEQ ID NO: 1; or
(2) And the sequence SEQ ID NO: 1 in 80% to 100% of amino acid sequence homology of the amino acid sequence encoding the same functional protein; or
(3) SEQ ID NO: 1 by adding, deleting or replacing one or more amino acids, and the expression product has the amino acid sequence similar to the sequence SEQ ID No: 1 the amino acid sequence of the expressed protein has the same activity.
Preferably, the N-terminal of the first sequence is connected with a second sequence, and the second sequence is:
(1) consisting of SEQ ID NO: 2; or
(2) And the sequence SEQ ID NO:2 in 80% to 100% of amino acid sequence homology of the amino acid sequence encoding the same functional protein; or
(3) SEQ ID NO:2 is added, deleted or substituted by one or more amino acids, and the expressed product has an amino acid sequence with the same activity as the expressed protein of the sequence SEQ ID No. 2.
Preferably, the N-terminal of the first sequence is connected with a third sequence, and the third sequence is:
(1) consisting of SEQ ID NO: 3; or
(2) And the sequence SEQ ID NO:3 in 80% to 100% of amino acid sequence homology of the amino acid sequence encoding the same functional protein; or
(3) SEQ ID NO:3 is added, deleted or substituted by one or more amino acids, and the expressed product has an amino acid sequence with the same activity as the expressed protein of the sequence SEQ ID No. 3.
According to another aspect of the invention, the application of the polypeptide is provided for preparing a medicament for treating acute kidney injury or diabetic nephropathy.
According to another aspect of the invention, the application of the polypeptide is provided, and the polypeptide is applied to preparation of medicines or health products for repairing DNA damage.
According to another aspect of the invention, there is provided a pharmaceutical composition comprising a polypeptide of claim and a pharmaceutically acceptable excipient.
According to another aspect of the present invention, there is provided a process for the preparation of a pharmaceutical composition comprising admixing a polypeptide according to any one of claims 1 to 3 and at least one pharmaceutically acceptable excipient.
In general, the above technical solutions contemplated by the present invention can achieve the following advantageous effects compared to the prior art.
The research finds that the 11 peptide, the 22 peptide containing the 11 peptide amino acid sequence and the 32 peptide can inhibit inflammation up-regulation caused by ischemia-reperfusion injury of the kidney of a C57BL/6 mouse and aggravation of DNA injury, wherein the 11 peptide and the 32 peptide can have a relatively obvious protective effect on acute kidney injury, the 11 peptide has a particularly obvious effect, and the 22 peptide also has a protective effect on the ischemia-reperfusion injury of the kidney to a certain extent.
The 32 peptide and 11 peptide of the present invention can inhibit DNA damage caused by renal ischemia-reperfusion by inhibiting DNA damage proteins such as p-ATR, p-chk1, p-h2a.x, and the like; can inhibit the up-regulation of inflammatory factors and the infiltration of inflammatory cells caused by renal ischemia reperfusion; can reduce apoptosis caused by renal ischemia reperfusion; can inhibit kidney morphology deterioration caused by renal ischemia-reperfusion, fibrosis related gene up-regulation and fibrin deposition. While the 22 peptide was able to alleviate these conditions to some extent, the 32 peptide and the 11 peptide showed better effects, especially the 11 peptide was significant.
Drawings
FIG. 1 is the amino acid sequences of the 11, 22 and 32 peptides of the invention;
FIG. 2 is a graph of the relative mRNA levels of inflammatory genes Kim1, Ilb, Icam1, Tnfa and DNA damage and apoptotic proteins for groups of cells following administration of the 11, 22 and 32 peptides of the invention;
FIG. 3 is a test of inhibition of H/R-induced DNA damage and apoptosis by peptides 11, 22 and 32 of the present invention;
FIG. 4 is a graph of cell viability, DNA damage-associated protein and apoptosis protein assays following administration of peptides 11, 22 and 32 of the present invention;
FIG. 5 is a design of an animal experiment;
FIG. 6 is a renal function test following administration of 11, 22 and 32 peptides of the invention;
FIG. 7 is a test of apoptosis-related proteins following administration of 11, 22 and 32 peptides of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The invention provides a polypeptide, wherein the amino acid sequence of the polypeptide comprises a first sequence which is:
(1) consisting of SEQ ID NO: 1; or
(2) And the sequence SEQ ID NO: 1 in 80% to 100% of amino acid sequence homology of the amino acid sequence encoding the same functional protein; or
(3) SEQ ID NO: 1 by adding, deleting or replacing one or more amino acids, and the expression product has the amino acid sequence similar to the sequence SEQ ID No: 1 the amino acid sequence of the expressed protein has the same activity.
Preferably, the amino acid sequence of the polypeptide of the invention may be: the N end of the first sequence is connected with a second sequence, and the second sequence is as follows:
(1) consisting of SEQ ID NO: 2; or
(2) And the sequence SEQ ID NO:2 in 80% to 100% of amino acid sequence homology of the amino acid sequence encoding the same functional protein; or
(3) SEQ ID NO:2 is added, deleted or substituted by one or more amino acids, and the expressed product has an amino acid sequence with the same activity as the expressed protein of the sequence SEQ ID No. 2.
Preferably, the amino acid sequence of the polypeptide of the invention may also be: the N end of the first sequence is connected with a third sequence, and the third sequence is as follows:
(1) consisting of SEQ ID NO: 3; or
(2) And the sequence SEQ ID NO:3 in 80% to 100% of amino acid sequence homology of the amino acid sequence encoding the same functional protein; or
(3) SEQ ID NO:3 is added, deleted or substituted by one or more amino acids, and the expressed product has an amino acid sequence with the same activity as the expressed protein of the sequence SEQ ID No. 3.
The polypeptide can be applied to the preparation of medicines for treating acute kidney injury or diabetic nephropathy, or the preparation of medicines or health-care products for repairing DNA injury.
The polypeptide of the invention is mixed with at least one pharmaceutically acceptable excipient to prepare the pharmaceutical composition.
In one of the preferable embodiments, the present invention designs and constructs 11 peptide (with the sequence of CMPLHSRVPFP-COOH) having carboxyl at the C-terminal, 22 peptide (with the sequence of KLRKHNCLQRRCMPLHSRVPFP-COOH) and 32 peptide (QRPVNLTMRRKLRKHNCLQRRCMPLHSRVPFP-COOH) including the amino acid sequence of 11 peptide, and the structures are shown in FIG. 1.
The C57BL/6 mice used in the examples of the invention were purchased from Hubei animal centers and the 11, 22 and 32 peptides of the invention were synthesized according to standard solid phase polypeptide synthesis procedures. The polypeptide synthesis direction is from C end to N end, firstly, the resin is swelled, and chlorine resin is used; then attaching the first amino acid to the resin; the first amino acid is attached to the resin and requires double amino, i.e. the amino acid reacts with the resin twice; subsequent removal (deprotection) of the amino terminal Fmoc group of the amino acid; repeating the steps of condensation, washing, deprotection, washing and condensation, and connecting amino acids one by one from the C end to the N end according to a polypeptide sequence until a required peptide fragment is synthesized; the desired 11-, 22-and 32-peptides were synthesized by resin deswelling and drying, peptide cleavage and purification of the crude peptide.
The 32 peptide and 11 peptide of the present invention can inhibit DNA damage caused by renal ischemia-reperfusion by inhibiting DNA damage proteins such as p-ATR, p-chk1, p-h2a.x, and the like; can relieve the up-regulation of inflammatory factors and the infiltration of inflammatory cells caused by renal ischemia reperfusion; can reduce apoptosis caused by renal ischemia reperfusion; can relieve kidney morphology deterioration caused by renal ischemia-reperfusion, fibrosis related gene up-regulation and fibrin deposition. While the 22 peptide was able to alleviate these conditions to some extent, the 32 peptide and the 11 peptide showed better effects, especially the 11 peptide was significant.
The following are examples:
example 1
The 11 peptide and the 32 peptide can inhibit inflammation, DNA damage and apoptosis caused by hypoxia reoxygenation injury of rat renal tubular cells (NRK-52E).
The method comprises the following specific operations: NRK-52E cells were treated and divided into normal group (CT group), hypoxia reoxygenation group (H/R group), hypoxia reoxygenation group to 32 peptides (E32 group), hypoxia reoxygenation group to 22 peptides (E22 group) and hypoxia reoxygenation group to 11 peptides (E11 group). The cells of each group were collected, and after RNA extraction, the relative mRNA levels of Kim1, Ilb, Icam1, Tnfa were examined for each group using a real-time quantitative PCR instrument (fig. 2A). The survival of the cells was examined by performing MTT assay (FIG. 2B) on each group of differently treated cells. NRK-52E cells were harvested, sonicated, and DNA damage-related proteins (p-ATR, p-Chk1, and p-H2A. X) and apoptosis-related proteins (caspase3 and C-caspase3) were detected by immunoblotting (FIGS. 2C and D). FIG. 2 analysis shows that the 32-, 22-and 11-peptides of the present invention can inhibit H/R-induced inflammation up-regulation, DNA damage and apoptosis.
The fluorescence intensity of p-h2a.x, a marker for DNA damage occurrence, was detected by immunofluorescence staining for each group of cells, and apoptosis of each group of cells was detected by TUNEL staining, and the results are shown in fig. 3.
As shown in FIGS. 2 and 3, under the condition of hypoxia reoxygenation, the relative mRNA levels of Kim1, Ilb, Icam1 and Tnfa of NRK-52E cells were significantly increased, and significantly decreased after the administration of 32 peptide and 11 peptide; there was also a reduction in the peptide to 22 to some extent. After administration of 32 and 11 peptides to NRK-52E cells after hypoxic reoxygenation treatment, there was a significant down-regulation of the protein levels of p-ATR, p-Chk1 and p-H2 A.X; the 22 peptide also improves hypoxia reoxygenation injury (H/R for short) to a certain extent. Through TUNEL staining and protein level detection of c-caspase3, 32 peptide and 11 peptide can obviously relieve the increase of apoptosis caused by hypoxia-reoxygenation injury (H/R for short) of cells.
Example 2
The 32 peptide and 11 peptide can inhibit DNA damage induced by Adriamycin (ADR) to renal tubular cells (NRK-52E)
The method comprises the following specific operations: NRK-52E cells were treated and divided into normal group (PBS group), ADR treatment (ADR group), 32 peptides after ADR treatment (E32 group), 22 peptides after ADR treatment (E22 group) and 11 peptides after ADR treatment (E11 group). The survival of the cells was examined by performing MTT assay on each group of differently treated cells (FIG. 4A). NRK-52E cells were harvested, sonicated, and DNA damage-related proteins (p-ATR, p-Chk1, and p-H2A. X) and apoptosis-related proteins (caspase3 and C-caspase3, PARP-1, and C-PARP-1) were detected by immunoblotting (see FIGS. 4B and C).
The results are shown in FIG. 4, where p-ATR, p-Chk1 protein levels were significantly down-regulated after ADR treatment with NRK-52E cells 32 and 11 peptides. There was a certain increase after administration of 22 peptides. It was found that administration of 32, 22 and 11 peptides reduced cell death caused by ADR by MTT assay. A significant reduction in c-caspase3 and c-PARP-1 was observed following administration of peptides 32 and 11 by immunoblotting, indicating that peptides 32 and 11 improved ADR-induced apoptosis.
Example 3
The polypeptide can inhibit the kidney morphology change, inflammation and fibrosis caused by C57BL/6 mouse kidney ischemia reperfusion (I/R for short).
The method comprises the following specific operations: before formal experiments, the injection dosage of the series of polypeptides is performed, and after the series of polypeptides are injected, all physiological indexes of a mouse are normal, so that the series of polypeptides are considered to be safe.
Mice weighing around 25g were divided into three groups: control mice group (CT group), kidney ischemia-reperfusion mice group (I/R group), kidney ischemia-reperfusion mice group given 32 peptides (E32 group) and kidney ischemia-reperfusion mice group given 11 peptides (E11 group). The group of renal ischemia-reperfusion mice underwent 45 min I/R surgery. The control mice group (CT group) and the renal ischemia reperfusion mice group (I/R group) were injected with phosphate buffer intraperitoneally twice a day. The group of 32 peptides (group E32) and the group of 11 peptides (group E11) were injected with 1.2mol of 32 peptides and 11 peptides per kg body weight twice a day for three days. Three days after the experiment, the kidneys were taken to measure weight and blood was collected, and the experimental design is shown in fig. 5.
As shown in fig. 6 and table 1, the total amount of urine, proteinuria, creatinine content and nitrogen content in urine were significantly increased by 24h urine collection after three days of I/R injury in mice, and the administration of 32 peptide and 11 peptide was able to better alleviate the increase of these renal function indices (table 1). Detecting the change of mouse kidney tissues; compared with the CT group, the I/R injury causes severe tubular injury such as extensive tubular necrosis, shedding of tubular cells, and the like. Scoring tissue sections by semi-quantitative showed that 32 and 11 peptides were able to significantly increase the score of damaged kidneys (fig. 6A). Through expression detection of a marker F4/80 of all macrophages, the infiltration of the macrophages is obviously increased after the I/R injury of the kidney, and the 32 peptide and the 11 peptide can relieve the infiltration, so that the 32 peptide and the 11 peptide can relieve the inflammation to a certain extent (figure 6B). The 32 and 11 peptides were found to protect mice with I/R injury from significant fibrotic degeneration by analysis of fibrotic markers such as collagen deposition (Masson stain for Masson stain), smooth muscle agonist (SAM) and Vimentin (Vimentin for short) (FIG. 6C). Experimental tests show that the 32 peptide and the 11 peptide have obvious improvement effect, the 22 peptide has certain improvement effect but slightly less effect than the 32 peptide and the 11 peptide, and the 11 peptide has the best effect.
TABLE 1, 32 peptide and 11 peptide effects on various indicators of renal function
Example 4
32 and 11 peptides are capable of inhibiting renal I/R injury-induced DNA damage response and apoptosis
The method comprises the following specific operations: mice weighing around 25g were divided into three groups: control mice group (CT group), kidney ischemia-reperfusion mice group (I/R group), kidney ischemia-reperfusion mice group given 32 peptides (E32 group) and visceral ischemia-reperfusion mice group given 11 peptides (E11 group). Mouse kidneys were embedded in paraffin and cut into 5 μ M thick sections, followed by immunohistochemical staining and TUNEL staining. The kidney is taken to grind and ultrasonically crack, and 20ug of the kidney is loaded to carry out an immunoblotting experiment to detect the apoptosis-related protein.
The results are shown in FIG. 7, and immunoblotting showed that p-ATR, p-Chk1 and p-H2A.X in CT group were almost undetectable at protein level; when I/R injury occurs in the kidney, p-ATR, p-Chk1 and p-H2A.X are obviously up-regulated in protein level. The 32, 22 and 11 peptides were able to inhibit the kidney I/R injury-induced upregulation of p-Chk1 and p-H2 A.X. Peptide 11 showed stronger inhibition of the increase in p-ATR and p-Chk1 protein levels induced by renal I/R injury compared to peptides 32 and 22 (fig. 7A). The staining results of renal epidermal cells showed that 32 peptide and 11 peptide inhibited p-h2a.x staining deepened by renal I/R injury (fig. 7C). The kidney I/R injury was able to upregulate C-caspase3, while peptides 32 and 11 were able to downregulate I/R injury-induced upregulation of C-caspase3 (FIG. 7B), and the TUNEL staining results were also consistent (FIG. 7C), indicating that peptides 32 and 11 are indeed able to inhibit renal I/R injury-induced apoptosis.
It will be understood by those skilled in the art that the foregoing is only a preferred embodiment of the present invention, and is not intended to limit the invention, and that any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the scope of the present invention.
SEQUENCE LISTING
<110> university of science and technology in Huazhong
<120> polypeptide
<130>2017
<160>3
<170>PatentIn version 3.3
<210>1
<211>11
<212>PRT
<213> Artificial sequence
<400>1
Cys Met Pro Leu His Ser Arg Val Pro Phe Pro
1 5 10
<210>2
<211>11
<212>PRT
<213> Artificial sequence
<400>2
Lys Leu Arg Lys His Asn Cys Leu Gln Arg Arg
1 5 10
<210>3
<211>21
<212>PRT
<213> Artificial sequence
<400>3
Gln Arg Pro Val Asn Leu Thr Met Arg Arg Lys Leu ArgLys His Asn
1 5 10 15
Cys Leu Gln Arg Arg
20
Claims (6)
1. The application of the polypeptide is characterized in that the polypeptide is applied to the preparation of a medicament for treating acute kidney injury or diabetic nephropathy; the amino acid sequence of the polypeptide comprises a first sequence consisting of SEQ ID NO: 1.
2. The use of claim 1, wherein the first sequence is N-terminally linked to a second sequence consisting of SEQ ID NO:2, or a pharmaceutically acceptable salt thereof.
3. The use of claim 1, wherein the first sequence is N-terminally linked to a third sequence consisting of SEQ ID NO: 3.
4. The application of the polypeptide is characterized in that the polypeptide is applied to the preparation of a medicine or a health-care product for repairing DNA damage, the amino acid sequence of the polypeptide comprises a first sequence, and the first sequence is represented by SEQ ID NO: 1.
5. The use of claim 4, wherein the first sequence is N-terminally linked to a second sequence consisting of SEQ ID NO:2, or a pharmaceutically acceptable salt thereof.
6. The use of claim 4, wherein the first sequence is N-terminally linked to a third sequence consisting of SEQ ID NO: 3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710223327.9A CN106831945B (en) | 2017-04-07 | 2017-04-07 | Polypeptide and application thereof in treating acute kidney injury |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710223327.9A CN106831945B (en) | 2017-04-07 | 2017-04-07 | Polypeptide and application thereof in treating acute kidney injury |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106831945A CN106831945A (en) | 2017-06-13 |
| CN106831945B true CN106831945B (en) | 2020-05-19 |
Family
ID=59147301
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710223327.9A Active CN106831945B (en) | 2017-04-07 | 2017-04-07 | Polypeptide and application thereof in treating acute kidney injury |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106831945B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107182937B (en) * | 2017-07-13 | 2021-07-16 | 广州市中医医院 | Construction method of in-vivo hypoxia-type diabetes mellitus early-stage animal model |
| CN110128506B (en) * | 2019-05-22 | 2021-03-30 | 中国药科大学 | Oligopeptide and application thereof |
| CN110669105B (en) * | 2019-10-31 | 2021-06-11 | 华中科技大学 | Long-acting polypeptide construction and application thereof in resisting acute kidney injury and diabetic complication nephropathy |
| CN112210001A (en) * | 2020-10-25 | 2021-01-12 | 兰州大学 | Polypeptide fragment ELA13 and application thereof |
| CN115974976B (en) * | 2022-11-23 | 2024-06-04 | 华中科技大学 | Antagonistic polypeptide and application thereof in preparing acute kidney injury resisting medicine |
| CN116617368A (en) * | 2023-05-30 | 2023-08-22 | 杭州师范大学 | Application of Elabela in vascular endothelial cell aging resistance |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1342686A (en) * | 2000-09-12 | 2002-04-03 | 上海博德基因开发有限公司 | Polypeptide-human kidney-specific protein 35.53 and polynucleotide for cocing it |
| CN1381498A (en) * | 2001-04-18 | 2002-11-27 | 上海博德基因开发有限公司 | Polypeptide-DNA bad damage repair protein -10.45 and polynucleotide for coding it |
| WO2015084264A1 (en) * | 2013-12-03 | 2015-06-11 | Agency For Science, Technology And Research | Polypeptides, nucleic acids and uses thereof |
| CN106243212A (en) * | 2016-07-29 | 2016-12-21 | 华中科技大学 | A kind of recombiant protein and application thereof |
-
2017
- 2017-04-07 CN CN201710223327.9A patent/CN106831945B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1342686A (en) * | 2000-09-12 | 2002-04-03 | 上海博德基因开发有限公司 | Polypeptide-human kidney-specific protein 35.53 and polynucleotide for cocing it |
| CN1381498A (en) * | 2001-04-18 | 2002-11-27 | 上海博德基因开发有限公司 | Polypeptide-DNA bad damage repair protein -10.45 and polynucleotide for coding it |
| WO2015084264A1 (en) * | 2013-12-03 | 2015-06-11 | Agency For Science, Technology And Research | Polypeptides, nucleic acids and uses thereof |
| CN106243212A (en) * | 2016-07-29 | 2016-12-21 | 华中科技大学 | A kind of recombiant protein and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 《Apelin多肽对胰脏和肾脏损伤的保护机制研究》;陈红;《中国博士学位论文全文数据库医药卫生科技辑》;20150715;摘要以及说明书第88页最后一段 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106831945A (en) | 2017-06-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106831945B (en) | Polypeptide and application thereof in treating acute kidney injury | |
| EP3062881B1 (en) | Cancer models and associated methods | |
| KR101669140B1 (en) | Peptides having Anti-obesity and Anti-Diabetes Effects and Use Thereof | |
| TWI642682B (en) | Glucagon analogues | |
| KR102359396B1 (en) | Peptide having angiogenesis inhibitory activity and composition containing same | |
| JP7090593B2 (en) | Methods and compositions for the treatment of cancer | |
| EP2664622B1 (en) | Polypeptides, nucleic acid molecule encoding polypeptides, and uses of polypeptides | |
| CN109912686B (en) | Stable polypeptide inhibitor targeting HDAC (Histone deacetylase) and application thereof | |
| US20100069297A1 (en) | Selective Inhibition of TLR4 Signaling | |
| AU2021221858A1 (en) | Compositions and methods for modulating AT2R activity | |
| EP2799445B1 (en) | Integrin blocker polypeptide for use in the treatment of rheumatoid arthrits | |
| CN111423502A (en) | Polypeptide, derivative thereof and application thereof in preparation of anti-pulmonary fibrosis drugs | |
| CN103764669A (en) | Anti-inflammatory pharmaceutical products | |
| US20180250358A1 (en) | Ghrh agonists for the treatment of ischemic disorders | |
| NZ578956A (en) | Treatment of trauma hemorrhage with short oligopeptides | |
| CN107629114B (en) | Polypeptide, derivative thereof and application thereof in preparation of anti-pulmonary fibrosis drugs | |
| US7638481B2 (en) | Treatment of spinal cord injury | |
| WO2014160508A1 (en) | Methods and compositions for treating cancer and inflammatory diseases | |
| CN110669105B (en) | Long-acting polypeptide construction and application thereof in resisting acute kidney injury and diabetic complication nephropathy | |
| CN114599395A (en) | Methods of treating multifocal cancers | |
| EP3333177B1 (en) | Multi-target compound with anticoagulation and antiplatelet activity, preparation method therefor, and use thereof | |
| WO2017147044A1 (en) | Peptides and methods for treatment of neurodegenerative diseases | |
| WO2010137012A1 (en) | Peptide therapy for amphiregulin mediated diseases | |
| EP2623512A1 (en) | Peptide capable of binding to immunoglobulin | |
| CN114206369A (en) | Methods of treating lower urinary tract symptoms using phenanthroline trifluoroacetate peptides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |