CN111499691A - ACE inhibitory peptide P1, application thereof and preparation method thereof - Google Patents
ACE inhibitory peptide P1, application thereof and preparation method thereof Download PDFInfo
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- CN111499691A CN111499691A CN202010345459.0A CN202010345459A CN111499691A CN 111499691 A CN111499691 A CN 111499691A CN 202010345459 A CN202010345459 A CN 202010345459A CN 111499691 A CN111499691 A CN 111499691A
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Images
Classifications
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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
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/06—Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Abstract
The invention discloses an ACE inhibitory peptide P1 with the amino acid sequence of FN L RMQ, the application of ACE inhibitory peptide P1 in auxiliary blood pressure lowering drugs or auxiliary blood pressure lowering functional foods and a preparation method of the ACE inhibitory peptide P1, wherein the ACE inhibitory peptide P1 obtained by the invention is extracted from puffer fish skin, has strong binding capacity with ACE enzyme and high activity, can be effectively used in blood pressure lowering drugs or functional foods to assist in lowering blood pressure, and has the advantages of high specificity and small toxic and side effects.
Description
Technical Field
The invention relates to the technical field of biology, and in particular relates to ACE inhibitory peptide P1. The invention also relates to application of the ACE inhibitory peptide and a preparation method thereof.
Background
Blood pressure regulation in humans is mainly controlled by the angiotensin system (RAS) and the kinin system (KKS), and Angiotensin Converting Enzyme (ACE) plays a key role in these two systems. ACE is a carboxydipeptidase enzyme widely distributed in mammalian tissues and is present in vascular epithelial cells primarily in the form of membrane-bound extracellular enzymes. In the RAS system, ACE is capable of converting physiologically inactive Angiotensin i (Ang i) into Angiotensin ii (Ang ii) having a boosting activity. In the KKS system, ACE can degrade bradykinin into inactive fragments, leading to vasoconstriction and resulting in elevated blood pressure. At present, hypertension is mainly treated by inhibiting ACE, and related researches show that some natural bioactive peptides separated from animals, plants and dairy products have the effects of inhibiting ACE activity and reducing blood pressure. Compared with the traditional antihypertensive drugs, the natural active peptides have the advantages of high specificity, small toxic and side effects, good curative effect, larger dosage of available drugs and the like.
The research on the preparation of ACE inhibitory peptide by enzymolysis includes a preparation method of the ACE inhibitory peptide which is prepared by taking food proteins such as milk, cheese, soybean, vegetable, wheat and the like as raw materials and carrying out enzymolysis by protease. EIJI et (antibiotic converting enzyme and inhibiting activity of the short peptides derived from the foods pro-proteins [ J ]. Nippon Shuhin Kagaku Kogaku Kaishi,1996,43(7):
839-840.) 12 kinds of food protein are hydrolyzed, it is found that the ACE inhibitory peptide prepared by enzymolysis of aquatic animal protein such as fish, shrimp and crab has a blood pressure lowering activity superior to other food protein.
ACE inhibitory peptides are inactive in the parent protein but can be released from the parent protein by enzymatic hydrolysis. Because the amino acid composition and the structure of the ACE inhibitory peptide are greatly different, the amino acid composition is not fixed or unified, and the components of a proteolysis product in food are quite complex, so that the separation and extraction difficulty of the proteolysis product is greatly increased.
The ACE inhibitory peptide activity detection method mainly comprises two methods of in vivo detection and in vitro experiment. In vitro assays commonly use IC50Shows ACE inhibitor inhibitory activity, inhibitor IC50The smaller the activity, the higher the activity.
Sunmei Ling et al in article "separation and purification of ACE inhibitory peptide in sea cucumber decoction" (proceedings of university of Dalian industries, 2019, 1 month) adopt macroporous tree adsorption method to separate sea cucumber decoction zymolyte polypeptide, and use p18 reversed phase silica gel column and L H-20 sephadex column to separate and purify ACE inhibitory peptide from the most active component, obtain 2 polypeptide monomers, IC with ACE inhibitory activity500.74 and 1.77mg/m L, respectively.
The patent with publication number CN108129561A discloses an ACE inhibitory peptide, which is prepared by virtually enzyme-cutting large yellow croaker actin to obtain a certain amount of peptide sequence, screening an unreported tripeptide sequence to predict toxicity, water solubility and ADMET properties, performing molecular docking by using discovery software, and finally screening to obtain tripeptide His-Glu-Arg (HER), identifying the in vitro ACE inhibitory activity of the tripeptide HER by using an RP-HP L C method50The value was 1.82. + -. 0.06 mM.
With the opening and development of the globefish processing and utilizing market, a large amount of byproducts (such as fish skin, fish head, fish viscera and the like) of the globefish after processing and utilizing are discarded as wastes or processed into animal feeds, so that huge pressure can be brought to the environment, negative effects can be brought to the society, and fish skin resources are greatly wasted. Therefore, the method makes full use of the nutritional ingredients in the puffer fish to develop various products with high added values, and brings new virtuous development to the whole puffer fish market. Research shows that the protein content of the fish skin is higher than that of the muscle, the collagen content in the fish skin can be more than 80% of the total protein content, and the protein of the fish skin also contains a small amount of albumin, adhesive protein, globulin and mucin besides the collagen which is mainly fibrous. At present, no report related to the extraction of ACE inhibitory peptide from puffer fish is available.
Disclosure of Invention
The invention aims to provide ACE inhibitory peptide P1 extracted from puffer fish skin, which has strong binding capacity with ACE enzyme and high activity and can be applied to auxiliary blood pressure lowering medicines or functional foods.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention discloses an ACE inhibitory peptide P1, the amino acid sequence of which is FN L RMQ.
Further, it has a molecular weight of 807.97Da, IC50It was 0.47. mu.M.
The invention discloses application of the ACE inhibitory peptide P1 in an auxiliary blood pressure lowering medicine or an auxiliary blood pressure lowering functional food.
The invention also discloses a preparation method of the ACE inhibitory peptide P1, which comprises the following steps:
s1, adding protease into the puffer fish skin for enzymolysis, wherein the enzymolysis temperature is controlled to be 50-60 ℃, the enzyme-substrate ratio is 2-4%, the pH value is 11-12, and the enzymolysis time is 5-7 h.
S2, carrying out primary filtration on the enzymolysis product, and removing residues to obtain clear polypeptide enzymolysis liquid.
S3, selecting a polyether sulfone ultrafiltration membrane to carry out ultrafiltration separation on the polypeptide enzymolysis liquid, dividing the collagen enzymolysis polypeptide into a plurality of ultrafiltration components, and freeze-drying the polypeptide liquid with different molecular weight distributions to obtain the polypeptide freeze-dried powder.
S4, weighing a proper amount of polypeptide freeze-dried powder with different molecular weights, respectively preparing polypeptide solutions, measuring the ACE inhibition rate of the polypeptide solutions, and screening to obtain the polypeptide freeze-dried powder with the strongest ACE inhibition activity.
S5, performing mass spectrometry on the screened polypeptide freeze-dried powder by adopting L C-MS/MS, and analyzing the mass spectrometry result by adopting mass spectrometry software to obtain a plurality of polypeptide sequences.
S6, performing molecular docking on the polypeptide sequence and the ACE protein through software, converting a 2D structure of the polypeptide into a 3D structure through energy minimization before docking, and screening to obtain the polypeptide sequence with strong binding capacity with the ACE protein.
S7, performing solid phase synthesis on the screened polypeptide sequence, and screening the polypeptide sequence with high activity to obtain the ACE inhibitory peptide P1.
In step S1, the enzymolysis temperature is 55 ℃, the enzyme-substrate ratio is 2%, the pH is 12, and the enzymolysis time is 6 h.
Preferably, in step S3, a polyethersulfone ultrafiltration membrane with a cut-off amount of 1kDa and 5kDa is selected to perform ultrafiltration separation on the polypeptide hydrolysate, the collagen enzymolysis polypeptide is divided into three ultrafiltration components with Mw <1kDa, 1kDa < Mw <5kDa and Mw >5kDa, and the three polypeptide solutions with different molecular weight distributions are lyophilized to obtain the polypeptide lyophilized powder.
Preferably, the mass spectrometry conditions in step S5 are PepMap RP L C C18 for the column, positive ion mode, scanning range of m/z 300-.
The invention has the following beneficial effects: the ACE inhibitory peptide P1 prepared by the method has good affinity with ACE enzyme, higher activity and IC50The value is 0.47 mu M, and the extract can be applied to development of therapeutic drugs or functional foods for assisting blood pressure reduction. And because the ACE inhibitory peptide P1 is extracted from the fish skin of the puffer fish, compared with the traditional antihypertensive drug, the ACE inhibitory peptide P1 has the advantages of high specificity and small toxic and side effects.
Drawings
FIG. 1 shows the effect of different enzymatic temperatures on ACE inhibition.
FIG. 2 shows the effect of different enzymatic hydrolysis times on ACE inhibition.
FIG. 3 shows the effect of different enzyme base ratios on ACE inhibition.
FIG. 4 is a graph of the effect of different pH on ACE inhibition.
FIG. 5 is a graph showing the effect of polypeptide fractions of different molecular weights on ACE inhibition.
FIG. 6 is an IC of polypeptide fractions of different molecular weights50The value is obtained.
FIG. 7 is a liquid chromatogram of polypeptide FN L RMQ of the invention.
FIG. 8 is a mass spectrum of the polypeptide FN L RMQ of the present invention.
Fig. 9 is a schematic diagram of the combination pattern of FN L RMQ with ACE.
Fig. 10 is a partially enlarged schematic view of fig. 9.
Detailed Description
In order to make the technical solutions of the present invention better understood by those skilled in the art, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.
The invention discloses an ACE inhibitory peptide P1, the amino acid sequence of which is FN L RMQ.
The preparation method of the ACE inhibitory peptide P1 comprises the following steps:
s1, adding protease into the puffer fish skin for enzymolysis, wherein the enzymolysis temperature is controlled to be 50-60 ℃, the enzyme-substrate ratio is 2-4%, the pH value is 11-12, and the enzymolysis time is 5-7 h. Preferably: the enzymolysis temperature is 55 ℃, the enzyme-substrate ratio is 2%, the pH is 12, and the enzymolysis time is 6 h.
The method takes the ACE inhibition rate as an assessment index, tests are carried out according to the conditions of different enzymolysis time, enzymolysis temperature, pH and enzyme addition amount of selected protease, and the influence of various factors on the ACE inhibition rate is examined. The specific experimental results are detailed below.
(1) Effect of different enzymatic hydrolysis temperatures on ACE inhibitory Activity
As shown in fig. 1, with the increase of the enzymolysis temperature, the ACE inhibitory activity of the collagen enzymolysis product is increased and then decreased, when the temperature reaches 65 ℃, the ACE inhibitory activity of the collagen enzymolysis product is sharply decreased, which may be due to the inactivation of protease caused by over-high temperature, resulting in the decrease of enzyme activity and the decrease of hydrolysis effect, thereby decreasing the clearance rate of DPPH by the collagen enzymolysis product. Therefore, 55 ℃ was determined as the optimum temperature for the enzymatic reaction.
(2) Effect of different enzymatic hydrolysis times on ACE inhibitory Activity
As shown in fig. 2, the effect of collagen enzymolysis products on ACE inhibitory activity also shows a trend of increasing and then decreasing with the increase of enzymolysis time, and the active peptide fragments may be continuously enzymolyzed for too long enzymolysis time, so that the inhibitory activity is reduced. Therefore, the optimum enzymolysis time is 6 h.
(3) Effect of different enzyme substrate ratios on ACE inhibitory Rate Activity
As can be seen from FIG. 3, the inhibition rate of the collagen enzymatic hydrolysate on ACE is firstly increased rapidly and then increased slowly with the increase of the enzyme concentration, and reaches the highest value when the enzyme base ratio is 4%, but the inhibition rate is not increased obviously from 2% to 3%. With further increasing enzyme dosage, ACE inhibition decreased instead, and the reaction reached equilibrium when the enzyme was saturated with substrate. The economic cost and the enzymolysis effect are comprehensively considered, and the enzyme-substrate ratio is better to be 2 percent.
(4) Effect of different pH on ACE inhibitory Activity
As shown in fig. 4, the effect of collagen enzymatic hydrolysis products on ACE inhibitory activity also shows a trend of increasing and then decreasing with increasing pH, which indicates that too high or too low pH inhibits the activity of protease, thereby decreasing the enzymatic hydrolysis efficiency, which is indicated by decreased ACE inhibition rate. Therefore, pH 12 was selected as an appropriate pH.
S2, carrying out primary filtration on the enzymolysis product, and removing residues to obtain clear polypeptide enzymolysis liquid. The primary filtration can be carried out by using eight layers of gauze.
S3, polyether sulfone ultrafiltration membranes with cutoff amounts of 1kDa and 5kDa are selected to carry out ultrafiltration separation on the polypeptide enzymolysis liquid, collagen enzymolysis polypeptides are divided into three ultrafiltration components with Mw <1kDa, 1kDa < Mw <5kDa and Mw >5kDa, and the three polypeptide liquids with different molecular weight distributions are freeze-dried to obtain polypeptide freeze-dried powder.
S4, weighing a proper amount of polypeptide freeze-dried powder with different molecular weights, preparing polypeptide solutions of 1mg/m L respectively, measuring the ACE inhibition rate of the polypeptide solutions, and screening to obtain the polypeptide freeze-dried powder with the strongest ACE inhibition activity.
The ACE inhibitory rate is determined by mixing a 100 mU L sample polypeptide solution with 50mU L of 50mU/m L0 ACE (ACE dissolved in 5000 mU L1 0.1 mol/L borate buffer containing 0.3 mol/L2 sodium chloride, pH 8.3), water bath at 37 ℃ for 10min, then adding 150 mU L5 mM HH L (prepared with 0.1 mol/L borate buffer containing 0.3 mol/L sodium chloride, pH 8.3), water bath at 37 ℃ for 30min, terminating the reaction by adding 200 mU L1.0 mol/L HCl, distilled water as a blank sample, during which ACE enzymolysis HH L releases hippuric acid whose concentration can be detected by HPLC UV detector at 228nm, wherein the formula for ACE inhibitory rate is:
wherein A isCKPeak area of hippuric acid as blank sample, ASThe peak area of hippuric acid which is an enzymolysis product.
From the results of FIGS. 5 and 6, it is clear that the inhibition ratio of Mw <1kDa is the best, the inhibition ratio of 1kDa < Mw <5kDa is the second lowest, and the inhibition ratio of Mw >5kDa on ACE is the weakest.
S5, performing mass spectrometry on the screened component polypeptide freeze-dried powder with Mw less than 1kDa by adopting L C-MS/MS, and analyzing the mass spectrometry result by adopting mass spectrometry software to obtain a plurality of polypeptide sequences.
The mass spectrometry conditions are that the chromatographic column is PepMap RP L C C18, the cation mode is adopted, the scanning range is m/z 300-1500 Da, and the mass spectrometry detection result of the emitter spray voltage 2 kV. is analyzed by PEAKS STUDIO software to obtain 82 polypeptide sequences.
S6, performing molecular docking on the polypeptide sequence and the ACE protein through MOE software, converting a 2D structure of the polypeptide into a 3D structure through energy minimization before docking, and screening to obtain the polypeptide sequence with strong binding capacity with the ACE protein.
The 3D structure of the protein ACE can be downloaded from the RCSB protein database (PDB ID: 1O 8A). The results of molecular docking are shown in table 1 below, where a smaller value (larger absolute value) for the docking score indicates a stronger binding capacity of the polypeptide to ACE enzyme and a higher probability of inhibiting the activity of ACE enzyme.
TABLE 1 molecular affinity size of different polypeptide sequences for ACE enzyme
S7, performing solid phase synthesis on the screened polypeptide sequence, and screening the polypeptide sequence with high activity to obtain the ACE inhibitory peptide P1.
Performing solid phase synthesis on the polypeptide sequence in the table 1, and screening to obtain a polypeptide sequence with high activity, namely 14 in the table and the amino acid sequence number of FN L RMQ, namely obtaining the ACE inhibitory peptide P1. the ACE inhibitory peptide P1 is subjected to liquid phase and mass spectrum measurement, as shown in figures 7 and 8, the molecular weight is 807.97Da, and IC is IC50The value was 0.47. mu.M. ACE inhibitory peptide P1 was soluble in ultrapure water, PBS and DMSO as shown in table 2.
TABLE 2 solubility test of ACE inhibitory peptide P1
| Solvent(s) | Solubility in water | Concentration of polypeptide |
| Ultrapure water | Soluble in water | ≦10mg/ml |
| 1X DPBS*(pH 7.1±0.1) | Soluble in water | ≦10mg/ml |
| DMSO | Soluble in water | ≦10mg/ml |
The polypeptide of the invention and ACE protein are subjected to molecular docking simulation experiments through MOE software, and the combination mode of ACE inhibitory peptide P1 and ACE can be obtained and is shown in figures 9 and 10. The nitrogen atom of the imidazolyl group of H353 in ACE forms a hydrogen bond with the sulfur atom of the sulfide group of M5 in P1. The oxygen atom of the carboxyl group of D453 in ACE forms a hydrogen bond with the nitrogen atom of the F1 backbone in P1. The nitrogen atom of the amino group of K454 in ACE forms a hydrogen bond with the oxygen atom of the N2 amide group in P1. The oxygen atom of the phenolic hydroxyl group of Y523 in ACE forms a hydrogen bond with the oxygen atom of the amide group of Q6 in P1. The carboxyl oxygen atom of E162 in ACE forms a salt bridge with the guanidino nitrogen atom of R4 in P1. The oxygen atom of the carboxyl group of D377 in ACE forms a salt bridge with the nitrogen atom of the guanidine group of R4 in P1. The carboxyl oxygen atom of E376 in ACE forms a salt bridge with the guanidino nitrogen atom of R4 in P1. Zn in ACE2+Form ionic contact with the oxygen atom of the amide group of Q6 in P1.
The butt joint simulation research shows that Zn in ACE2+E162, H353, E376, D377, D453, K454 and Y523 participate in binding to F1, N2, R4, M5 and Q6, and the residue of P1 interacts by ionic contact, salt bridge binding and hydrogen bonding. As shown in table 3 below.
TABLE 3 contact list of ACE inhibitory peptide P1 with ACE activity
| Chain A | Residue of | Chain B | Residue of | Type of interaction |
| ACE | His353 | P1 | M5 | Hydrogen bond interactions |
| ACE | Asp453 | P1 | F1 | Hydrogen bond interactions |
| ACE | Lys454 | P1 | N2 | Hydrogen bond interactions |
| ACE | Tyr523 | P1 | Q6 | Hydrogen bond interactions |
| ACE | Zn2+ | P1 | Q6 | Ionic bond |
| ACE | Glu162 | P1 | R4 | Salt bridge |
| ACE | Glu376 | P1 | R4 | Salt bridge |
| ACE | Asp377 | P1 | R4 | Salt bridge |
In conclusion, the ACE inhibitory peptide P1 prepared by the method has strong interaction with ACE enzyme and high activity, and can be applied to auxiliary blood pressure lowering medicines or auxiliary blood pressure lowering functional foods.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention.
Sequence listing
<110> Fujian provincial aquatic product research institute (Fujian aquatic product disease control center)
<120> ACE inhibitory peptide P1, application thereof and preparation method thereof
<160>1
<170>PatentIn version 3.5
<210>P1
<211>6
<212>PRT
<213> puffer fish
<400>P1
Phe Asn Leu Arg Met Gln
1 5
Claims (7)
- An ACE inhibitory peptide P1 characterized by the amino acid sequence FN L RMQ.
- 2. The ACE inhibiting peptide P1 of claim 1, having a molecular weight of 807.97Da, IC50It was 0.47. mu.M.
- 3. The use of the ACE inhibitory peptide P1 of claim 1 as an adjunctive blood pressure lowering drug or as a functional food for adjunctive blood pressure lowering.
- 4. The process for the preparation of ACE inhibiting peptide P1 according to claim 1, comprising the steps of:s1, adding protease into the puffer fish skin for enzymolysis, wherein the enzymolysis temperature is controlled to be 50-60 ℃, the enzyme-substrate ratio is 2-4%, the pH value is 11-12, and the enzymolysis time is 5-7 h;s2, primarily filtering the enzymolysis product, and removing residues to obtain clear polypeptide enzymolysis liquid;s3, selecting a polyether sulfone ultrafiltration membrane to carry out ultrafiltration separation on the polypeptide enzymolysis liquid, dividing the collagen enzymolysis polypeptide into a plurality of ultrafiltration components, and freeze-drying polypeptide liquid with different molecular weight distributions to obtain polypeptide freeze-dried powder;s4, weighing a proper amount of polypeptide freeze-dried powder with different molecular weights, respectively preparing polypeptide solutions, measuring the ACE inhibition rate of the polypeptide solutions, and screening to obtain the polypeptide freeze-dried powder with the strongest ACE inhibition activity;s5, performing mass spectrometry on the screened polypeptide freeze-dried powder by adopting L C-MS/MS, and analyzing the mass spectrometry result by adopting mass spectrometry software to obtain a plurality of polypeptide sequences;s6, performing molecular docking on the polypeptide sequence and the ACE protein through software, converting a 2D structure of the polypeptide into a 3D structure through energy minimization before docking, and screening to obtain a polypeptide sequence with strong binding capacity with the ACE protein;s7, performing solid phase synthesis on the screened polypeptide sequence, and screening the polypeptide sequence with high activity to obtain the ACE inhibitory peptide P1.
- 5. The method of claim 4, wherein the temperature of the enzymatic hydrolysis is 55 ℃, the ratio of the substrate to the enzyme is 2%, the pH is 12, and the enzymatic hydrolysis time is 6 hours in step S1.
- 6. The method for preparing ACE inhibitory peptide P1 according to claim 4, wherein in step S3 polyether sulfone ultrafiltration membranes with cut-off amounts of 1kDa and 5kDa are selected to perform ultrafiltration separation on the polypeptide hydrolysate, collagen enzymolysis polypeptides are divided into three ultrafiltration components with Mw <1kDa, 1kDa < Mw <5kDa and Mw >5kDa, and the three polypeptide liquids with different molecular weight distributions are lyophilized to obtain polypeptide lyophilized powder.
- 7. The method of claim 4, wherein the mass spectrometry conditions in step S5 are PepMap RP L C C18 as column, cation mode, scanning range m/z 300-1500 Da, and emitter spray voltage 2 kV.
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