CN112390877B - PEDF-derived polypeptide composition and application thereof in preparation of lung injury protection drugs - Google Patents
PEDF-derived polypeptide composition and application thereof in preparation of lung injury protection drugs Download PDFInfo
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- CN112390877B CN112390877B CN201910758301.3A CN201910758301A CN112390877B CN 112390877 B CN112390877 B CN 112390877B CN 201910758301 A CN201910758301 A CN 201910758301A CN 112390877 B CN112390877 B CN 112390877B
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Abstract
The invention discloses a PEDF-derived polypeptide composition and application thereof in preparing a medicament for protecting lung injury, wherein the PEDF-derived polypeptide composition is prepared from a polypeptide shown in SEQ ID NO:2 and the 34 amino acid sequence peptide shown in SEQ ID NO:3, and the 44 amino acid sequence peptide shown in the figure. The PEDF-derived polypeptide composition designed by the invention has good functional advantages, and has obvious effects of resisting inflammation, resisting vascular leakage, protecting alveolar epithelial cells and the like in acute lung injury and chronic non-injury. The derivative polypeptide composition has the advantages of small molecular weight, good treatment effect, easy absorption and poor antigenicity, can effectively avoid anaphylactic reaction and side effect generated when protein drugs are used, is easy to synthesize, obviously reduces the production cost and has higher clinical applicability.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to a PEDF-derived polypeptide composition and application thereof in preparation of a medicine for protecting lung injury.
Background
Various internal and external pathogenic factors can cause the destruction of the respiratory system and cause acute or chronic lung injury. Acute Lung Injury (ALI) is a common critical clinical condition, the incidence rate of China is 79/10 ten thousand, and the mortality rate is up to 68.5%.
ALI is a disease of alveolar epithelial cell and capillary endothelial cell injury caused by various directly or indirectly traumatic factors, and is manifested by diffuse interstitial pulmonary disease and alveolar edema, and acute hypoxic respiratory insufficiency. ALI occurs in association with neutrophil infiltration and release of cytokines and inflammatory mediators, hyperpermeability of the pulmonary vessels and damage of alveolar epithelial cells are important features of the disease.
A poor prognosis of ALI, or Chronic injury occurring on its basis, leads to the development of Chronic Lung Disease (CLD), idiopathic Pulmonary Fibrosis (IPF) being a common end result of a variety of diseases. The mean survival after IPF diagnosis is only 2.8 years, the mortality rate is higher than that of most tumors, and no effective treatment is available except for lung transplantation.
In conclusion, the prior art has poor effect of preventing and treating lung injury, and further technical means are needed to prevent and treat inflammation, vascular leakage and epithelial cell injury in the lung injury process.
Disclosure of Invention
This section is for the purpose of summarizing some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. In this section, as well as in the abstract and the title of the invention of this application, simplifications or omissions may be made to avoid obscuring the purpose of the section, the abstract and the title, and such simplifications or omissions are not intended to limit the scope of the invention.
The present invention has been made in view of the above-mentioned technical drawbacks.
Accordingly, in one aspect of the present invention, the present invention overcomes the deficiencies of the prior art by providing a composition of PEDF-derived polypeptides.
In order to solve the technical problems, the invention provides the following technical scheme: a PEDF-derived polypeptide composition: consisting of SEQ ID NO:2 and the 34 amino acid sequence peptide shown in SEQ ID NO:3, and the 44 amino acid sequence peptide shown in the figure.
As a preferred embodiment of the PEDF-derived polypeptide composition of the present invention: in the composition, the molar ratio of the 34 amino acid sequence peptide to the 44 amino acid sequence peptide is 1: (0.5-2).
As a preferred embodiment of the PEDF-derived polypeptide composition of the present invention: in the composition, the molar ratio of the 34 amino acid sequence peptide to the 44 amino acid sequence peptide is 1:1.
as a preferred embodiment of the PEDF-derived polypeptide composition of the present invention: the PEDF-derived polypeptide composition can be used for treating acute lung injury and chronic lung injury.
As another aspect of the present invention, the present invention overcomes the deficiencies of the prior art and provides the use of the PEDF-derived polypeptide composition for preparing a medicament for protecting lung injury.
As a preferred embodiment of the application of the PEDF-derived polypeptide composition of the present invention in the preparation of a medicament for protecting lung injury: the PEDF-derived polypeptide composition includes a salt of the PEDF-derived polypeptide composition.
As a preferred embodiment of the application of the PEDF-derived polypeptide composition of the present invention in preparing a medicament for protecting lung injury: the salt, including salts of the PEDF-derived polypeptide composition with organic acids, including acetic acid, lactic acid, maleic acid, citric acid, malic acid, ascorbic acid, succinic acid, benzoic acid, salicylic acid, methanesulfonic acid, toluenesulfonic acid, trifluoroacetic acid, or pamoic acid; the polymeric acid comprises tannic acid, carboxymethyl cellulose; the inorganic acid comprises halogen acid, sulfuric acid and phosphoric acid.
As a preferred embodiment of the application of the PEDF-derived polypeptide composition of the present invention in preparing a medicament for protecting lung injury: the lung injury comprises acute lung injury and chronic lung injury.
As a preferred embodiment of the application of the PEDF-derived polypeptide composition of the present invention in preparing a medicament for protecting lung injury: the medicament comprises loading the PEDF-derived polypeptide composition into a carrier.
As a preferred embodiment of the application of the PEDF-derived polypeptide composition of the present invention in the preparation of a medicament for protecting lung injury: the carrier comprises one or more of solvent, diluent, suspending agent, emulsifier, antioxidant, pharmaceutical preservative, colorant, flavoring agent, medium, oily base, and excipient.
The invention has the beneficial effects that: the PEDF-derived polypeptide composition designed by the invention has good functional advantages, and has obvious effects of resisting inflammation, resisting vascular leakage, protecting alveolar epithelial cells and the like in acute lung injury and chronic non-injury. The derivative polypeptide composition has the advantages of small molecular weight, good treatment effect, easy absorption and poor antigenicity, can effectively avoid anaphylactic reaction and side effect generated when protein drugs are used, is easy to synthesize, obviously reduces the production cost, and has higher clinical applicability.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the description below are only some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained according to the drawings without inventive labor. Wherein:
FIG. 1 is a graph of HE staining of lung tissue in rat acute lung injury induced by lipopolysaccharide according to example 1 of the present invention.
FIG. 2 is a photograph of a Cleaved Caspase-3 (cleared Caspase-3) immunoblot of the acute lung injury cell model of example 2 of the present invention.
FIG. 3 is a histogram showing the statistics of the Cleaved Caspase-3 (cleared Caspase-3) expression levels in the acute lung injury cell model of example 2 of the present invention.
FIG. 4 is a graph of HE staining of lung tissue in rats with chronic lung injury induced by bleomycin in example 3 of the present invention.
FIG. 5 is a graph showing Masson staining of lung tissue in rats with chronic lung injury induced by bleomycin in example 3 of the present invention.
FIG. 6 is a histogram showing the degree of fibrosis of chronic lung injury induced by bleomycin in rat in example 3 of the present invention.
FIG. 7 is an immunoblot of human lung fibroblast-expressed alpha-smooth muscle actin (. Alpha. -SMA) of example 4 of the invention.
FIG. 8 is a histogram showing the expression level of alpha-smooth muscle actin (alpha-SMA) expressed by fibroblasts of example 4 of the present invention.
FIG. 9 is an immunoblot of human endothelial cell expressed alpha-smooth muscle actin (alpha-SMA) of example 5 of the invention.
FIG. 10 is a histogram showing the expression level of alpha-smooth muscle actin (alpha-SMA) expressed by human endothelial cells in example 5 of the present invention.
Detailed Description
In order to make the aforementioned objects, features and advantages of the present invention comprehensible, embodiments accompanied with examples are described in detail below.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, however, the present invention may be practiced otherwise than as specifically described herein, and it will be appreciated by those skilled in the art that the present invention may be practiced without departing from the spirit and scope of the present invention and that the present invention is not limited by the specific embodiments disclosed below.
Furthermore, the references herein to "one embodiment" or "an embodiment" refer to a particular feature, structure, or characteristic that may be included in at least one implementation of the present invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.
All peptide sequences mentioned herein are written according to general convention with the N-terminal amino acid on the left and the C-terminal amino acid on the right. The short line between two amino acid residues indicates a peptide bond.
The compounds of the present invention may be provided in the form of pharmaceutically acceptable salts. Examples of preferred salts are those formed with pharmaceutically acceptable organic acids such as acetic acid, lactic acid, maleic acid, citric acid, malic acid, ascorbic acid, succinic acid, benzoic acid, salicylic acid, methanesulfonic acid, toluenesulfonic acid, trifluoroacetic acid or pamoic acid, as well as polymeric acids such as tannic acid or carboxymethylcellulose, and salts with inorganic acids such as hydrohalic acids (e.g., hydrochloric acid, sulfuric acid or phosphoric acid, etc.). Any method known to those skilled in the art to obtain pharmaceutically acceptable salts may be used.
For convenience in describing the invention, conventional and non-conventional abbreviations for the various amino acid residues are used. These abbreviations are familiar to those skilled in the art, but are listed below for clarity:
asp = D = aspartic acid; ala = a = alanine; arg = R = arginine;
asn = N = asparagine; gly = G = glycine; glu = E = glutamic acid;
gln = Q = glutamine; his = H = histidine; ile = I = isoleucine;
leu = L = leucine; lys = K = lysine; met = M = methionine;
phe = F = phenylalanine; pro = P = proline; ser = S = serine;
thr = T = threonine; trp = W = tryptophan; tyr = Y = tyrosine;
val = V = valine; cys = C = cysteine.
Example 1:
study of effect of PEDF on protection of lipopolysaccharide-induced acute lung injury in rats
Experimental animals: healthy adult Sprague Dawley (SD) rats weighing 230-250g were randomized into 3 groups, normal control, model, and treatment.
Animal models: a rat acute lung injury model is established by tracheal instillation of Lipopolysaccharide (LPS) aqueous solution (2 mg/kg), a normal control group is instilled with equal amount of physiological saline in a tracheal instillation manner, and a treatment group is instilled with LPS and PEDF mixed aqueous solution, wherein the LPS (2 mg/kg) and the PEDF (1 mg/kg).
The experimental results are as follows:
1. determination of the wet-to-dry weight ratio (W/D) of the lung tissue: after the animal model is established for 24 hours, the rat is killed by exsanguination of abdominal aorta, the left lung is taken out by opening the thoracic cavity, the left lung is cleaned by normal saline, and the left lung is weighed after being sucked dry by filter paper, so that the wet weight (W) of the lung tissue is obtained. The lung tissue was then placed in a 60 ℃ oven for 48h and weighed again to obtain the dry weight of lung tissue (D). The W/D value was calculated to reflect the degree of edema of the lung tissue. The results are shown in Table 1.
TABLE 1
| Group of | W/D value |
| Normal control group | 3.6±0.43 |
| Model set | 6.7±0.72* |
| Treatment group | 4.8±0.55* # |
P compared to normal control group<0.05; in comparison to the set of models, # P<0.05。P<0.05 indicated significant differences.
As shown in Table 1, compared with the normal control group, the W/D value of the model group is obviously increased, which indicates that the pulmonary tissue edema is serious, and compared with the W/D value of the PEDF treatment group, the W/D value of the model group is reduced, and the pulmonary tissue edema is not deep, which proves that the PEDF can effectively reduce the pulmonary tissue edema caused by acute lung injury.
2. Protein Permeability Index (PPI) assay: after 24h of animal model establishment, fresh blood was drawn through the abdominal main vein at 0.5ml, followed by abdominal aortic bleeding to sacrifice the rats, cervical skin was incised, trachea was exposed, and the lung bronchi were lavaged with sterile physiological saline (5 ml each, repeated 3 times) to obtain bronchoalveolar lavage fluid. The serum protein concentration and the bronchoalveolar lavage fluid protein concentration were measured using a total protein quantitative determination kit (commercially available), and the PPI value was calculated: (bronchoalveolar lavage fluid protein concentration/serum protein concentration) × 100 to reflect pulmonary vascular permeability. The results are shown in Table 2.
TABLE 2
| Group of | PPI value |
| Normal control group | 0.13±0.02 |
| Model set | 0.85±0.15* |
| Treatment group | 0.46±0.07*# |
P <0.05 compared to normal control group; compared to the model group, # P <0.05.P <0.05 indicates significant differences.
As shown in Table 2, compared with the normal control group, the PPI value of the model group is obviously increased, which indicates that the pulmonary vascular permeability is obviously increased, and the PPI value of the PEDF treatment group is reduced and the pulmonary vascular permeability is slightly increased compared with the model group, thus proving that the PEDF can effectively reduce the pulmonary vascular permeability of acute lung injury and protect the endothelial barrier.
3. Pathological observation of lung tissues: and (3) taking the right lung middle lobe of the rat, placing the right lung middle lobe of the rat in a 4% paraformaldehyde solution for fixation for 24 hours, then carrying out conventional paraffin-embedded section and HE staining, and observing the pathological condition of lung tissues of the rat in each group. The results are shown in FIG. 1.
As shown in FIG. 1, the normal control group had clear and intact lung tissue structure, smooth alveolar walls and no effusion or exudate in alveolar spaces; the lung tissue structure of the model group is disordered, the pulmonary interstitium is obviously widened, the basement membrane is broken and damaged, and a large amount of exudates and inflammatory cell infiltration can be seen in the alveolar cavity; compared with the model group, the treatment group has the advantages of obvious reduction of various pathological features, slight disorder of lung tissue structure, slight broadening of lung interstitium, complete pulmonary alveolus and no obvious effusion or exudate. PEDF treatment was shown to be effective in reducing lipopolysaccharide-induced acute lung injury in rats. Column 1A represents the normal control group, column 1B represents the model group, and column 1C represents the treatment group. Bar =50um.
Example 2:
research on TNF-alpha stimulated rat alveolar type II epithelial cell RLE-6TN protection effect of PEDF and polypeptide derived from PEDF
Test cells: rat alveolar type II epithelial cells (RLE-6 TN) were purchased from Gechenochi Biotech, inc. in Shanghai. The group was randomly divided into 6 groups, a normal control group, a model group, a PEDF group (amino acid sequence shown in SEQ ID NO: 1), a 34 peptide group (amino acid sequence shown in SEQ ID NO: 2), a 44 peptide group (amino acid sequence shown in SEQ ID NO: 3), a 34 peptide and 44 peptide mixed peptide group (mixed in a molar ratio of 1.
Cell model: an acute lung injury cell model is constructed by stimulating RLE-6TN cells (10 ng/mL) by using tumor necrosis factor (TNF-alpha), and is cultured routinely in a normal control group, a PEDF treatment group applies PEDF intervention (20 nmol/L) at the same time of administering the TNF-alpha, a 34 peptide treatment group applies 34 peptide intervention (20 nmol/L) at the same time of administering the TNF-alpha, a 44 peptide treatment group applies 44 peptide intervention (20 nmol/L) at the same time of administering the TNF-alpha, and a 34 peptide and 44 peptide mixed peptide treatment group applies 34 peptide and 44 peptide mixed peptide intervention (20 nmol/L) at the same time of administering the TNF-alpha.
The experimental results are as follows:
determination of the degree of apoptosis: after 36h after the cell model was established, the cells were harvested, 500. Mu.l of lysate (commercially available) was added to each 10cm dish, lysed 30min on ice or at 4 ℃ and centrifuged at 14000rpm for 20min at 4 ℃ and the supernatant was taken. Leave 15-20 μ l of sample for protein quantification and store the rest in a refrigerator at-20 ℃ for future use. Samples were incubated with protein treatment solution (commercially available) at 4:1, uniformly mixing, boiling for 10min to fully denature protein; naturally cooling, and storing at-20 deg.C for use.
The expression level of Cleaved Caspase-3 (cleaned Caspase-3) representing the degree of apoptosis was detected by Western Blot, and the quantitative protein analysis was performed by ImageJ software, and the statistical analysis was performed using the ratio of the gray level of the target protein to the gray level of the internal reference (. Beta. -tubulin). The results are shown in FIGS. 2 and 3.
As shown in FIGS. 2 and 3, the expression level of clear Caspase-3 in the model group was significantly increased as compared with that in the normal control group; compared with the model group, the PEDF group has obviously reduced clear Caspase-3 expression level; compared with a model group, the expression level of the cleared Caspase-3 in the 34 peptide group is not obviously changed; the expression level of the 44 peptide group is reduced compared with that of the model group, but is higher than that of the PEDF group; peptide 34 and peptide 44 the clear Caspase-3 expression level was lower than that of peptide 44 and slightly higher than that of PEDF. Proved that PEDF, 44 peptide and 34 peptide and 44 peptide mixed peptide can effectively protect alveolar epithelial cells and reduce apoptosis in acute lung injury. Column 2A represents the normal control group, column 2B represents the model group, column 2C represents the PEDF group, column 2D represents the 34 peptide group, column 2E represents the 44 peptide group, column 2F represents the 34 peptide and 44 peptide groups. P <0.05 compared to normal control group; compared to the model group, # P <0.05.P <0.05 indicates significant differences.
Example 3:
study of the protective effect of PEDF on bleomycin-induced chronic lung injury in rats
The experimental animals were randomly divided into 4 groups, normal control group, model group, sham-treated group, and treated group, as in example 1.
Animal model: a rat chronic lung injury model is established by tracheal instillation of bleomycin (5 mg/kg), a normal control group is given with equal amount of normal saline, a treatment group is given with equal amount of normal saline by tracheal instillation of PEDF (1 mg/kg) aqueous solution for three times every three days after the model is established, and a sham treatment group is given with equal amount of normal saline every three days.
The experimental results are as follows:
pathological observation of lung tissues: in the same manner as in example 1, the right middle lung lobe of rat was subjected to conventional paraffin-embedded section, HE staining, and Masson staining. HE staining is shown in FIG. 4 and Masson staining is shown in FIG. 5.
The degree of pulmonary fibrosis was classified as 4: grade 0 with no obvious change; grade 1 mild changes, with a range of lesions less than 20% of the total lung; grade 2 moderate changes, with lesion range of 20% -50% of the total lung; grade 3 severe changes, with a range of lesions over 50% of the total lung. The evaluation results are shown in FIG. 6.
The results are shown in fig. 4, 5, and 6: the normal control group has complete and clear lung tissue structure, normal pulmonary interstitium, no obvious effusion or exudate in the alveolar cavity, no inflammatory cell infiltration or fibroblast proliferation, and a small amount of collagen fiber deposition in large bronchus and large blood vessel; the pulmonary alveolar structures of the model group and the pseudo-treatment group are seriously damaged, the pulmonary spacing is obviously thickened, the pulmonary alveolar cavity is atrophied and collapsed, a large amount of inflammatory cell infiltration and fibroblast proliferation can be seen, a large amount of collagen fibers are deposited, and the pulmonary fibrosis degree is serious; the lung tissue structure of the PEDF group is complete and clear, the lung interstitium is slightly thickened, a small amount of inflammatory cell infiltration and a small amount of fibroblast hyperplasia can be seen, the collagen fiber deposition is less, and the degree of pulmonary fibrosis is obviously lighter than that of the model group and the pseudo-treatment group. PEDF was shown to be effective in reducing the degree of fibrosis associated with chronic lung injury. Column 4A/5A represents the normal control group, column 4B/5B represents the model group, column 4C/5C represents the sham-treated group, and column 4D/5D represents the treated group. Bar =50um. P <0.05 compared to normal control group; compared to the model group, # P <0.05.P <0.05 indicates significant differences.
Example 4:
research on activation of human lung fibroblast MRC-5 stimulated by TGF-beta 1 through PEDF and polypeptide derived from PEDF
Test cells: human lung fibroblasts (MRC-5) were purchased from Gechenochi Biotech, inc. in Shanghai, and randomly divided into 6 groups, normal control group, model group, PEDF group, 34 peptide group, 44 peptide group, 34 peptide and 44 peptide mixed peptide group.
The experimental results are as follows:
alpha-smooth muscle actin (alpha-SMA) expression amount determination: after 24h of cell model establishment, cell protein was extracted as in example 2, the expression level of α -SMA was detected by Western Blot, quantitative protein analysis was performed by ImageJ software, and statistical analysis was performed using the ratio of the gray level of the target protein to the gray level of the internal reference (. Beta. -tubulin). The results are shown in FIGS. 7 and 8.
As shown in fig. 7 and 8: compared with a normal control group, the alpha-SMA expression level of the model group is obviously increased; compared with a model group, the PEDF group has obviously reduced alpha-SMA expression level; the 34 peptide group slightly reduces the alpha-SMA expression compared with the model group, but has no statistical significance; the expression level of the 44 peptide group compared with that of the model group alpha-SMA has no obvious change; the 34 peptide and 44 peptide groups slightly reduced the expression level of alpha-SMA compared with the model group, but higher than that of PEDF group. The PEDF is proved to be capable of effectively inhibiting the activation of human lung fibroblasts and relieving the fibrosis degree in acute lung injury, but the effect of the derived polypeptide is not good enough.
Example 5:
research on PEDF and derived polypeptide thereof for inhibiting TGF-beta 1-stimulated endothelial intercellular substance transformation
Experimental cells: human Coronary Microvascular Endothelial Cells (HCMECs) were purchased from Sciencell, and randomly divided into 6 groups: normal control group, model group, PEDF group, 34 peptide group, 44 peptide group, 34 peptide and 44 peptide mixed peptide group.
Cell model: an endothelial mesenchymal transition model was constructed by stimulating cells (10 ng/ml) with transforming growth factor (TGF-. Beta.1), and cultured routinely in a normal control group, the PEDF group was administered with PEDF intervention (20 nmol/L) simultaneously with TGF-. Beta.1, the 34 peptide group was administered with 34 peptide intervention (20 nmol/L) simultaneously with TGF-. Beta.1, the 44 peptide group was administered with 44 peptide intervention (20 nmol/L) simultaneously with TGF-. Beta.1, and the 34 peptide and 44 peptide mixed peptide group was administered with 34 peptide and 44 peptide mixed peptide intervention (20 nmol/L) simultaneously with TGF-. Beta.1.
The experimental results are as follows:
alpha-smooth muscle actin (alpha-SMA) assay: after 48h of cell model establishment, cell protein was extracted as in example 2, the expression level of α -SMA was detected by Western Blot, quantitative protein analysis was performed by ImageJ software, and statistical analysis was performed using the ratio of the gray level of the target protein to the gray level of the internal reference (. Beta. -tubulin). The results are shown in FIGS. 9 and 10.
As shown in fig. 9 and 10, compared with the normal control group, the expression level of the model group α -SMA is significantly increased; compared with a model group, the PEDF group has obviously reduced alpha-SMA expression level; 34, compared with the model group, the alpha-SMA expression level is reduced, but is not as remarkable as that of the PEDF group; the expression level of the 44 peptide group compared with that of the model group alpha-SMA has no obvious change; the alpha-SMA expression of the 34 peptide and 44 peptide groups is lower than that of the 44 peptide group and slightly higher than that of the PEDF group. Proved that the PEDF, the 44 peptide and the 34 peptide and 44 peptide mixed peptide can effectively inhibit the mesenchymal transition of endothelial cells and reduce the source of fibroblasts in the chronic lung injury.
The PEDF holoprotein has larger molecules, higher synthesis cost and poorer clinical applicability, and the derivative polypeptide composition has small molecular weight, good treatment effect, easy absorption and poor antigenicity, can effectively avoid the anaphylactic reaction and side effect generated when protein drugs are used, is easy to synthesize, obviously reduces the production cost and has higher clinical applicability.
The invention relates to an amino acid sequence:
PEDF amino acid sequence (SEQ ID NO: 1):
MQALVLLLCIGALLGHSSCQNPASPPEEGSPDPDSTGALVEEEDPFFKVPVNKLAAAVSNFGYDLYRVRSSMSPTTNVLLSPLSVATALSALSLGADERTESIIHRALYYDLISSPDIHGTYKELLDTVTAPQKNLKSASRIVFEKKLRIKSSFVAPLEKSYGTRPRVLTGNPRLDLQEINNWVQAQMKGKLARSTKEIPDEISILLLGVAHFKGQWVTKFDSRKTSLEDFYLDEERTVRVPMMSDPKAVLRYGLDSDLSCKIAQLPLTGSMSIIFFLPLKVTQNLTLIEESLTSEFIHDIDRELKTVQAVLTVPKLKLSYEGEVTKSLQEMKLQSLFDSPDFSKITGKPIKLTQVEHRAGFEWNEDGAGTTPSPGLQPAHLTFPLDYHLNQPFIFVLRDTDTGALLFIGKILDPRGP
34 peptide amino acid sequence (44-77 aa) (SEQ ID NO: 2):
DPFFKVPVNKLAAAVSNFGYDLYRVRSSMSPTTN
44 peptide amino acid sequence (78-121 aa) (SEQ ID NO: 3):
VLLSPLSVATALSALSLGAEQRTESIIHRALYYDLISSPDIHGT
it should be noted that the above-mentioned embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, which should be covered by the claims of the present invention.
Sequence listing
<110> Xuzhou university of medicine
<120> PEDF-derived polypeptide composition and application thereof in preparation of lung injury protection drugs
<140> 2019107583013
<141> 2019-08-16
<160> 3
<170> SIPOSequenceListing 1.0
<210> 1
<211> 418
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 1
Met Gln Ala Leu Val Leu Leu Leu Cys Ile Gly Ala Leu Leu Gly His
1 5 10 15
Ser Ser Cys Gln Asn Pro Ala Ser Pro Pro Glu Glu Gly Ser Pro Asp
20 25 30
Pro Asp Ser Thr Gly Ala Leu Val Glu Glu Glu Asp Pro Phe Phe Lys
35 40 45
Val Pro Val Asn Lys Leu Ala Ala Ala Val Ser Asn Phe Gly Tyr Asp
50 55 60
Leu Tyr Arg Val Arg Ser Ser Met Ser Pro Thr Thr Asn Val Leu Leu
65 70 75 80
Ser Pro Leu Ser Val Ala Thr Ala Leu Ser Ala Leu Ser Leu Gly Ala
85 90 95
Asp Glu Arg Thr Glu Ser Ile Ile His Arg Ala Leu Tyr Tyr Asp Leu
100 105 110
Ile Ser Ser Pro Asp Ile His Gly Thr Tyr Lys Glu Leu Leu Asp Thr
115 120 125
Val Thr Ala Pro Gln Lys Asn Leu Lys Ser Ala Ser Arg Ile Val Phe
130 135 140
Glu Lys Lys Leu Arg Ile Lys Ser Ser Phe Val Ala Pro Leu Glu Lys
145 150 155 160
Ser Tyr Gly Thr Arg Pro Arg Val Leu Thr Gly Asn Pro Arg Leu Asp
165 170 175
Leu Gln Glu Ile Asn Asn Trp Val Gln Ala Gln Met Lys Gly Lys Leu
180 185 190
Ala Arg Ser Thr Lys Glu Ile Pro Asp Glu Ile Ser Ile Leu Leu Leu
195 200 205
Gly Val Ala His Phe Lys Gly Gln Trp Val Thr Lys Phe Asp Ser Arg
210 215 220
Lys Thr Ser Leu Glu Asp Phe Tyr Leu Asp Glu Glu Arg Thr Val Arg
225 230 235 240
Val Pro Met Met Ser Asp Pro Lys Ala Val Leu Arg Tyr Gly Leu Asp
245 250 255
Ser Asp Leu Ser Cys Lys Ile Ala Gln Leu Pro Leu Thr Gly Ser Met
260 265 270
Ser Ile Ile Phe Phe Leu Pro Leu Lys Val Thr Gln Asn Leu Thr Leu
275 280 285
Ile Glu Glu Ser Leu Thr Ser Glu Phe Ile His Asp Ile Asp Arg Glu
290 295 300
Leu Lys Thr Val Gln Ala Val Leu Thr Val Pro Lys Leu Lys Leu Ser
305 310 315 320
Tyr Glu Gly Glu Val Thr Lys Ser Leu Gln Glu Met Lys Leu Gln Ser
325 330 335
Leu Phe Asp Ser Pro Asp Phe Ser Lys Ile Thr Gly Lys Pro Ile Lys
340 345 350
Leu Thr Gln Val Glu His Arg Ala Gly Phe Glu Trp Asn Glu Asp Gly
355 360 365
Ala Gly Thr Thr Pro Ser Pro Gly Leu Gln Pro Ala His Leu Thr Phe
370 375 380
Pro Leu Asp Tyr His Leu Asn Gln Pro Phe Ile Phe Val Leu Arg Asp
385 390 395 400
Thr Asp Thr Gly Ala Leu Leu Phe Ile Gly Lys Ile Leu Asp Pro Arg
405 410 415
Gly Pro
<210> 2
<211> 34
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 2
Asp Pro Phe Phe Lys Val Pro Val Asn Lys Leu Ala Ala Ala Val Ser
1 5 10 15
Asn Phe Gly Tyr Asp Leu Tyr Arg Val Arg Ser Ser Met Ser Pro Thr
20 25 30
Thr Asn
<210> 3
<211> 44
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 3
Val Leu Leu Ser Pro Leu Ser Val Ala Thr Ala Leu Ser Ala Leu Ser
1 5 10 15
Leu Gly Ala Glu Gln Arg Thr Glu Ser Ile Ile His Arg Ala Leu Tyr
20 25 30
Tyr Asp Leu Ile Ser Ser Pro Asp Ile His Gly Thr
35 40
Claims (1)
1. The application of the PEDF-derived polypeptide composition in preparing the medicine for protecting acute lung injury is characterized in that:
the PEDF-derived polypeptide composition consists of SEQ ID NO:2 and the 34 amino acid sequence peptide shown in SEQ ID NO:3, and a 44 amino acid sequence peptide shown in the specification;
the molar ratio of the 34 amino acid sequence peptide to the 44 amino acid sequence peptide is 1:0.5 to 2.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910758301.3A CN112390877B (en) | 2019-08-16 | 2019-08-16 | PEDF-derived polypeptide composition and application thereof in preparation of lung injury protection drugs |
| CN202010716340.XA CN111760019B (en) | 2019-08-16 | 2019-08-16 | Application of PEDF in preparation of medicine for protecting chronic lung injury |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910758301.3A CN112390877B (en) | 2019-08-16 | 2019-08-16 | PEDF-derived polypeptide composition and application thereof in preparation of lung injury protection drugs |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010716340.XA Division CN111760019B (en) | 2019-08-16 | 2019-08-16 | Application of PEDF in preparation of medicine for protecting chronic lung injury |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112390877A CN112390877A (en) | 2021-02-23 |
| CN112390877B true CN112390877B (en) | 2022-10-04 |
Family
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| Application Number | Title | Priority Date | Filing Date |
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| CN201910758301.3A Active CN112390877B (en) | 2019-08-16 | 2019-08-16 | PEDF-derived polypeptide composition and application thereof in preparation of lung injury protection drugs |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112390877B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101014358A (en) * | 2003-10-29 | 2007-08-08 | 约翰·霍普金斯大学 | Biological activity of pigment epithelium-derived factor and methods of use |
| CN107602691A (en) * | 2017-08-22 | 2018-01-19 | 徐州医科大学 | Purposes of the derivative polypeptide series of pigment epidermal derived factors for protection ischemic myocardium |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060189519A1 (en) * | 2002-09-26 | 2006-08-24 | Karl Volz | Anti-angiogenic fragments fo pigment epithelium-derived factor (pedf) |
| CA2982909A1 (en) * | 2005-08-05 | 2007-02-15 | Araim Pharmaceuticals, Inc. | Tissue protective peptides and uses thereof |
| EP2015781A4 (en) * | 2005-09-12 | 2009-12-23 | Univ Johns Hopkins | Compositions having antiangiogenic activity and uses thereof |
| US20090069241A1 (en) * | 2006-02-15 | 2009-03-12 | Yale University | Compositions and Methods for Use of Pigment Epithelial Derived Factor (PEDF) Peptide Fragments |
| EP2895502B1 (en) * | 2012-09-17 | 2018-09-05 | Mackay Memorial Hospital | Use of pedf-derived polypeptides for treating alopecia and/or hair depigmentation |
| CN108392626B (en) * | 2018-03-02 | 2021-10-01 | 董红燕 | Application of PEDF and derivatives thereof in preparation of reconstructed coronary artery reserve collateral microcirculation drugs and drug screening method thereof |
-
2019
- 2019-08-16 CN CN201910758301.3A patent/CN112390877B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101014358A (en) * | 2003-10-29 | 2007-08-08 | 约翰·霍普金斯大学 | Biological activity of pigment epithelium-derived factor and methods of use |
| CN107602691A (en) * | 2017-08-22 | 2018-01-19 | 徐州医科大学 | Purposes of the derivative polypeptide series of pigment epidermal derived factors for protection ischemic myocardium |
Non-Patent Citations (1)
| Title |
|---|
| PEDF expression regulates the proangiogenic and proinflammatory phenotype of the lung endothelium.;Shin ES, et al.;《Am J Physiol Lung Cell Mol Physiol.》;20140401;第306卷(第7期);摘要 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112390877A (en) | 2021-02-23 |
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