CN108752421B - Synthetic polypeptide, synthetic method and application thereof, and gene for encoding synthetic polypeptide - Google Patents
Synthetic polypeptide, synthetic method and application thereof, and gene for encoding synthetic polypeptide Download PDFInfo
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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Abstract
The invention discloses a synthetic polypeptide, a synthetic method and application thereof, and a gene for coding the synthetic polypeptide. The amino acid sequence of the polypeptide is: Leu-Val-Tyr-Pro is shown in a sequence table SEQ ID No. 1. The polypeptide of the invention is synthesized by a solid phase synthesis method by using a polypeptide synthesizer. The polypeptide of the invention passes an oxygen radical absorption capacity experiment (ORAC), and the result shows that the polypeptide has certain antioxidant capacity. The polypeptide is applied to an ethanol-induced liver injury cell model, and an MTT detection method is used for detecting the protection effect of the polypeptide on LO2 cells, so that the result shows that the polypeptide can inhibit the survival rate reduction of the ethanol-induced LO2 cells, has a certain liver protection effect, and can be applied to the protection of alcoholic liver diseases.
Description
Technical Field
The invention relates to the technical field of preventing and treating alcoholic liver diseases, in particular to a synthetic polypeptide with a protective effect on ethanol-induced hepatocyte (LO2) damage, application thereof and a gene for encoding the synthetic polypeptide.
Background
Alcoholic Liver Disease (ALD) is a chronic liver disease caused by long-term heavy drinking. Early stages usually manifest as fatty liver, which in turn can progress to alcoholic hepatitis, alcoholic liver fibrosis and alcoholic cirrhosis. The disease is common in European and American countries, and the incidence rate of the disease in China is increased in recent years. According to epidemiological investigation in some regions, the disease rate of alcoholic liver disease of Chinese adults is 4% -6%, so that the human health is seriously affected.
The pathogenesis of the alcoholic liver disease is relatively complex, and researches find that the alcoholic liver disease is related to various factors such as ethanol and acetaldehyde, which is a metabolite of the ethanol, oxidative stress, endotoxin, lipid peroxidation, cell apoptosis and the like. The liver is the most important metabolic organ of ethanol in human body, and research shows that Alcohol Dehydrogenase (ADH), liver Microsome Ethanol Oxidation System (MEOS) and Catalase (CAT) are three pathways involved in ethanol metabolism. The enzyme at the core of MEOS is cytochrome P4502E1(CYP2E1), which is induced by ethanol to be activated, participates in most of ethanol metabolism, and generates excessive Reactive Oxygen Species (ROS), and ROS accumulated in cells attacks cell membranes and mitochondria to cause structural and functional damage of cells, so that redox in cells is unbalanced, and thus liver cell damage or apoptosis is caused, and further, liver cell inflammation, liver fibrosis, liver cell necrosis and other pathological changes can occur. Genetic factors are thought to be closely related to the occurrence of alcoholic liver disease, but specific genetic markers have not been established; sex factors also affect the incidence, and women with the same alcohol intake are more susceptible to alcoholic liver disease than men, and are associated with lower Alcohol Dehydrogenase (ADH) content in women. Therefore, the development of effective anti-hangover and anti-hangover drugs is an important subject for research and study by medical researchers at home and abroad. At present, the treatment methods of alcoholic liver are gradually increased, for example, colchicine, propyl thiouracil, lipid-lowering drugs, endotoxin-resisting agents and other therapies have certain effects, but the drugs have certain toxic and side effects.
Bioactive peptides are structural and functional fragments that constitute proteins, and are peptide compounds that are beneficial to the vital functions of the living organism or have physiological effects. The source of the compound is very wide, and the compound can be sourced from various organisms and also can be obtained by artificial synthesis or bioengineering methods. The peptide drugs are derived from natural polypeptides, artificially modified polypeptides and artificially synthesized polypeptides. The artificially synthesized polypeptide has the characteristics of definite structure, easy modification and improvement and qualitative determination. Moreover, many scientific studies have demonstrated that synthetic polypeptides have a very good role in the treatment of certain diseases. The polypeptide has the advantages of easy digestion and absorption, high edible safety, little toxic and side effect, good processing performance and the like, also has various physiological functions of reducing blood pressure, reducing blood fat, improving immunoregulation, hormone regulation and the like, is a treasure house for obtaining natural resources of medicines, has attracted wide attention at home and abroad for the research of bioactive peptides, and a plurality of polypeptides with bioactivity are widely applied to practice in the fields of biological pharmacy, vaccines, health care products and the like.
Disclosure of Invention
In order to overcome the defects and shortcomings of the prior art and improve the diversity and safety of liver-protecting medicines, the invention aims to provide a synthetic polypeptide, application thereof and a gene for coding the synthetic polypeptide. The synthetic polypeptide has antioxidant activity, can reduce the toxicity of ethanol on liver cells (LO2), and can improve the cell survival rate, and can be used as a functional factor for developing medicines and health products.
A synthetic polypeptide has an amino acid sequence of Leu-Val-Tyr-Pro, wherein Leu is an amino acid corresponding residue of leucine, Val is an amino acid corresponding residue of valine, Tyr is an amino acid corresponding residue of tyrosine, and Pro is an amino acid corresponding residue of proline, and is shown in a sequence table SEQ ID No. 1.
The sequence of the corresponding gene of the gene for coding the synthetic polypeptide is shown in a sequence table SEQ ID No. 2.
The synthetic polypeptide provided by the invention can be applied to the preparation of foods, health-care products and medicines for preventing and treating the spermatogenic liver diseases.
The synthesis of the amino acid sequence polypeptide comprises the steps of firstly screening resin, and then adopting a standard Fmoc scheme to select 2-chlorotrityl chloride resin (2-chlorotrityl chloride resin) for solid phase synthesis; meanwhile, the polypeptide can also be synthesized by a genetic engineering technology, the coding gene is accessed into a vector, the vector is transcribed into a prokaryotic expression system escherichia coli or a eukaryotic expression system yeast for expression, and then the target polypeptide is separated and purified.
Furthermore, the invention adopts an oxygen radical absorption capacity experiment (ORAC) to detect the antioxidant activity of the synthetic polypeptide, the synthetic polypeptide has strong hydrogen supply capacity and higher ORAC activity, and simultaneously acts on an ethanol-induced hepatocyte (LO2) injury model, so that the liver protection effect is obvious.
Compared with the prior art, the invention has the following advantages and beneficial effects:
the polypeptide of the invention passes an oxygen radical absorption capacity experiment (ORAC), and the result shows that the polypeptide has certain antioxidant capacity. The polypeptide is applied to an ethanol-induced liver injury cell model, and an MTT detection method is used for detecting the protection effect of the polypeptide on LO2 cells, so that the result shows that the polypeptide can inhibit the reduction of the survival rate of the ethanol-induced LO2 cells, has a certain liver protection effect, can be applied to the protection of alcoholic liver diseases, is a nontoxic, healthy and safe compound, and has a very wide prospect in the application of foods, health care products and medicines for preventing and treating the essential liver diseases.
Drawings
FIG. 1 is a molecular structural diagram of a polypeptide with the sequence of Leu-Val-Tyr-Pro.
FIG. 2 is an HPLC chart of the polypeptide.
FIG. 3 is an ESI-MS graph of a polypeptide.
FIG. 4 is a graph comparing the effect of polypeptides on cell viability of LO2 at different concentrations.
Figure 5 is a graph comparing the effect of polypeptides at different concentrations on ethanol-induced cytotoxicity of LO 2.
FIG. 6 is a graph comparing the effect of polypeptides on the mitochondrial membrane potential of ethanol-induced LO2 cells.
Detailed Description
The invention discloses a polypeptide and application thereof. The technical personnel can modify the technological parameters appropriately to realize the method by taking the contents of the invention as reference. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. The synthetic polypeptide provided by the present invention, its synthetic method and application are further described below.
Example 1: solid phase synthesis of polypeptides
1. Resin model selection
(1) A standard Fmoc (Fmoc) protocol was used, which used 0.0125mmol, 2-chlorotrityl chloride resin (2-chlorotrityl chloride resin), 0.3mol of the first Fmoc protected amino acid was added according to the sequence characteristics of the amino acid sequence Leu-Val-Tyr-Pro, DCC and 5% (mass fraction) DMAP were added to the reactor for oscillation reaction, and NMP was used to wash the resin to remove excess protected amino acid. The efficiency of the first amino acid linkage to the resin, i.e., the coupling ratio, was determined (as shown in Table 1).
(2) 0.0125mmol of 4- (hydroxymethyl) phenoxymethyl polystyrene resin (Wang resin) was selected and the efficiency of the first amino acid linkage to the resin, i.e., the coupling ratio, was determined as described above (Table 1).
TABLE 1
| Type of resin | Coupling ratio (%) |
| 2-chlorotrityl chloride resin | 96.23±0.88 |
| Wang resin | 90.89±1.01 |
2. Synthesis process
Adopting a standard Fomc scheme, selecting 2-chlorotrityl chloride resin with high coupling rate, extending peptide chains from the C end to the N end one by one according to the sequence characteristics of an amino acid sequence Leu-Val-Tyr-Pro, adding 0.3mol of Fmoc protective amino acid, adding HOBT to activate and protect carboxyl of the amino acid in each step of condensation, adopting 20% piperidine DMF (15ml/g) in each step of condensation, treating for 20min, and removing the Fmoc protective group. After peptide side chain synthesis, the resin-containing peptide chain was added to the following reaction solution: dichloromethane (99%) trifluoroacetic acid (1%) (volume fraction) to cleave the peptide chain from the resin. The polypeptide was added to the reaction solution again: trifluoroacetic acid (94.5%), ethylenediamine tartrate (2.5%), distilled water (2%) and TIS (1%) (volume fraction) for 2h, and removing side chain protecting groups. The synthesized polypeptide is purified by high performance liquid chromatography, the purity reaches more than 99%, and the structure is identified by ESI-MS (as shown in figure 2 and figure 3), and table 2 is a relevant parameter corresponding to the peak appearance sequence in figure 2.
TABLE 2
| Order of appearance | Retention time (min) | Peak area | Area ratio (%) |
| 1 | 8.438 | 69127 | 0.550561 |
| 2 | 9.207 | 6409 | 0.051044 |
| 3 | 9.336 | 12456748 | 99.21156 |
| 4 | 9.657 | 23459 | 0.186839 |
Example 2: ORAC value determination of synthetic Polypeptides
The reaction was carried out in a 75mmol/L potassium phosphate buffer (pH 7.4) environment, and the specific experimental procedures were as follows: mu.L of synthetic polypeptide, GSH solution and Trolox standard solution (6.25, 12.5, 25, 50. mu.M) are added into each micropore of a 96-pore plate, 200. mu.L of FL solution (95.68. mu. mol/mL) is added into each pore, the mixture is incubated at 37 ℃ for 20min, then 20. mu.L of AAPH solution (119.4. mu. mol/mL) is rapidly added into each pore by using a multi-channel pipette, the micropore plate is placed in a micropore plate detector, the excitation wavelength is 485nm, the emission wavelength is 538nm for continuous measurement, the fluorescence intensity of each pore is measured every 2min, and the measurement is carried out for 90 times. The ORAC experiment required setting of two control groups, FL fluorescence natural decay control without added free radical (-AAPH) and free radical action control in the absence of antioxidant (+ AAPH). A standard curve was plotted using Trolox as a standard, and ORAC values of samples were expressed as Trolox equivalent, and the ORAC values of synthetic polypeptides, GSH, are shown in Table 3.
TABLE 3
| Sample name | ORAC value (mol TE/mol) |
| GSH | 0.32±0.06 |
| Leu-Val-Tyr-Pro | 2.18±0.28 |
Example 3: liver protection application of synthetic polypeptide acting on ethanol-induced hepatocyte damage model
LO2 cells in logarithmic growth phase were seeded in 96-well cell plates at 5X 10 per well3Placing the cells in CO2After culturing in an incubator for 24h, the experimental group is added with culture solution with synthetic polypeptide concentration of 0.25, 0.5, 0.75, 1, 1.25mmol/L respectively, the blank control group is added with equal amount of culture solution, each group is provided with 3 parallels, and the groups are put back into the incubator to continue culturing for 24 h. mu.L of LMTT solution (5mg/mL) was added to each well, incubated in an incubator for 4h, the supernatant was discarded, 150. mu.L of DMSO was added to each well, and the absorbance OD was measured at 490nm for each well. Calculating the survival rate of each group of cells treated with different ethanol concentrations, as shown in fig. 4, the effect of the polypeptide on ethanol-induced LO2 cytotoxicity, and testing the statistical difference between the synthetic peptide and the control group without the peptide and the statistical difference between different doses of the polypeptide by using one-way ANOVA; wherein represents P<0.01, # denotes P<0.05。
Example 3: liver protection application of synthetic polypeptide acting on ethanol-induced hepatocyte damage model
LO2 cell concentration in logarithmic growth phase was adjusted to 5X 103After one/mL, the cells were seeded in 96-well plates at 100. mu.L per well and placed in a cell incubator for 24h for re-attachment. Adding 0.5mmol/L synthetic polypeptide culture solution into experimental group, pre-incubating for 24h, adding equal amount of culture solution into model group, incubating for 24h, discarding supernatant, adding 0.5mmol/L synthetic polypeptide culture solution into experimental groupmmol/L synthetic polypeptide and 0.8mol/L ethanol culture solution, adding 0.8mol/L ethanol culture solution into the model group, and continuously culturing for 24h, wherein the blank control group is always cultured with the culture solution. mu.L of MTT solution (5mg/mL) was added to each well, incubated in an incubator for 4h, the supernatant was discarded, 150. mu.L of DMSO was added to each well, and the absorbance OD was measured at 490nm for each well. The survival rate of each group of cells was calculated as shown in fig. 5.
Example 4: liver protection application of synthetic polypeptide acting on ethanol-induced hepatocyte damage model
LO2 cell concentration in logarithmic growth phase was adjusted to 5X 103After one/mL, the cells were seeded in 96-well plates at 100. mu.L per well and placed in a cell incubator for 24h for re-attachment. Adding a synthetic polypeptide culture solution with the concentration of 1mmol/L into an experimental group for pre-incubation for 24h, adding an equivalent culture solution into a model group, incubating for 24h, discarding supernatant, adding a culture solution simultaneously containing 1mmol/L of synthetic polypeptide and 0.8mol/L of ethanol into the experimental group, adding a culture solution simultaneously containing 0.8mol/L of ethanol into the model group, continuing to culture for 24h, and always culturing the blank control group with the culture solution. mu.L of MTT solution (5mg/mL) was added to each well, incubated in an incubator for 4h, the supernatant was discarded, 150. mu.L of DMSO was added to each well, and the absorbance OD at 490nm was measured for each well to calculate the viability of each group of cells, as shown in FIG. 5.
Example 6: mitochondrial membrane potential detection and evaluation of protective effect of polypeptide on ethanol-induced LO2 cells
JC-1 is a mitochondrial fluorescent probe which can be polymerized in a mitochondrial matrix depending on the electric potential. In normal mitochondria, the transmembrane potential of the mitochondria is high, and JC-1 forms a polymer under the action of potential energy to emit orange red fluorescence. When mitochondria are disordered, the mitochondrial membrane potential is reduced and even lost, JC-1 can not aggregate in a mitochondrial matrix, and can only disperse in cells in a monomer form to show green fluorescence. The change of mitochondrial membrane potential can be detected according to the change of fluorescence color of cells after JC-1 staining. LO2 cells in logarithmic growth phase were seeded in 12-well cell plates at 5X 10 per well4Placing the cells in CO2After culturing for 24h in an incubator, the experimental group is pre-incubated for 24h with 1mmol/L synthetic polypeptide, the model group is added with the same amount of culture solution and incubated for 2hAnd 4h, discarding the supernatant, adding a culture solution containing 1mmol/L synthetic polypeptide and 0.8mol/L ethanol into the experimental group, adding a culture solution containing 0.8mol/L ethanol into the model group, continuously culturing for 24h, and always culturing the blank control group by using the culture solution. Then digesting with pancreatin, collecting cells in each hole, centrifuging, adding 0.5ml JC-1 staining working solution for staining for half an hour, washing with PBS solution for 2 times, and detecting. The excitation light can be set to be 490nm and the emission light can be set to be 530nm when detecting JC-1 monomer; when JC-1 polymer is detected, the excitation light can be set to 525nm and the emission light to 590nm, and the detection result is shown in FIG. 6.
The low dose group (0.5mM) and the high dose group (1mM) of the synthetic polypeptide were used for the dry prognosis of the cell model, compared with the model group, the cell survival rate of LO2 cells was significantly improved (P <0.01), and the effect of the high dose group was more significant (P <0.05) than that of the low dose group, and was concentration-dependent. The result of mitochondrial membrane potential experiments shows that ethanol has higher mitochondrial transmembrane potential of 36.5% of cells, can enable JC-1 to form a polymer and emit orange-red fluorescence, and 72% of cells can form the JC-1 polymer and emit orange-red fluorescence after the pre-incubation of the synthetic polypeptide, which indicates that the synthetic polypeptide can protect the reduction of mitochondrial membrane potential caused by the induction of LO2 cells by ethanol and alleviate the influence of mitochondrial dysfunction caused by ethanol. The results show that the synthetic polypeptide disclosed by the invention can inhibit the survival rate of LO2 cells induced by ethanol from being reduced, has a certain liver protection effect, and can be applied to the protection of the direction of alcoholic liver diseases.
Sequence listing
<110> university of southern China's science
<120> a synthetic polypeptide, its synthetic method and use, and gene encoding the synthetic polypeptide
<140> 2018105115601
<141> 2018-05-24
<160> 2
<170> SIPOSequenceListing 1.0
<210> 1
<211> 4
<212> PRT
<213> Artificial Synthesis (Artificial sequence)
<400> 1
Leu Val Tyr Pro
1
<210> 2
<211> 12
<212> DNA
<213> Artificial Synthesis (Artificial sequence)
<400> 2
Claims (3)
1. The application of the synthetic polypeptide in preparing the medicine for preventing and treating the alcoholic liver diseases is characterized in that the amino acid sequence of the synthetic polypeptide is Leu-Val-Tyr-Pro which is shown as SEQ ID No. 1 in a sequence table, wherein Leu is the corresponding residue of leucine, Val is the corresponding residue of valine, Tyr is the corresponding residue of tyrosine, and Pro is the corresponding residue of proline.
2. Use according to claim 1, characterized in that: the synthetic polypeptide has hydrogen supply capacity and ORAC activity, and has liver protecting effect on ethanol-induced LO2 liver cell injury model.
3. Use according to claim 1, characterized in that: the preparation of the synthetic polypeptide comprises: firstly, screening resin, and then carrying out solid-phase synthesis by adopting a standard Fmoc scheme and 2-chlorotrityl chloride resin; or synthesized by a genetic engineering technology, the coding gene is accessed into a vector, the vector is transcribed into a prokaryotic expression system escherichia coli or a eukaryotic expression system yeast for expression, and then the target polypeptide is separated and purified to obtain the polypeptide.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101481412A (en) * | 2009-02-09 | 2009-07-15 | 吉林大学 | Polypeptide with antineoplastic function, encoding gene and use thereof |
| CN106727626A (en) * | 2017-01-19 | 2017-05-31 | 南京师范大学 | Application of 1,6 diphosphofructose in treatment alcoholic hepatic injury medicine is prepared |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101481412A (en) * | 2009-02-09 | 2009-07-15 | 吉林大学 | Polypeptide with antineoplastic function, encoding gene and use thereof |
| CN106727626A (en) * | 2017-01-19 | 2017-05-31 | 南京师范大学 | Application of 1,6 diphosphofructose in treatment alcoholic hepatic injury medicine is prepared |
Non-Patent Citations (3)
| Title |
|---|
| Hepatoprotective peptides purified from Corbicula fluminea and its effect against ethanol-induced LO2 cells injury;Jiaoyan Ren等;《International Journal of Food Science and Technology》;20200526;第1-10页 * |
| 河蚬多肽分离纯化、结构鉴定及其 对乙醇诱导 LO2 细胞损伤的保护机制研究;尚帅明;《中国优秀硕士学位论文全文数据库工程科技I辑》;20190115;全文 * |
| 河蚬酶解物对乙醇诱导肝细胞LO2 损伤的保护作用;任娇艳等;《华南理工大学学报》;20171231;第45卷(第12期);第21-26页 * |
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