CN116970036A - Maca protein source active peptide with angiotensin converting enzyme inhibitory activity and application thereof - Google Patents
Maca protein source active peptide with angiotensin converting enzyme inhibitory activity and application thereof Download PDFInfo
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- CN116970036A CN116970036A CN202310984088.4A CN202310984088A CN116970036A CN 116970036 A CN116970036 A CN 116970036A CN 202310984088 A CN202310984088 A CN 202310984088A CN 116970036 A CN116970036 A CN 116970036A
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- converting enzyme
- angiotensin converting
- maca
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- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 description 1
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Microbiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention discloses a maca protein source active peptide with angiotensin converting enzyme inhibitory activity and application thereof; the amino acid sequences of the maca protein source active peptide with the angiotensin converting enzyme inhibitory activity are RSRGVFF, LGHPVFRNK, HGSCNYR, KANLGFRF, GGGHKRLY and SSYLGRN respectively. According to the invention, active peptides are screened through virtual prediction and molecular docking, and the angiotensin converting enzyme inhibitory activity is verified through high performance liquid chromatography, so that six polypeptides with the angiotensin converting enzyme inhibitory activity are obtained. The six angiotensin converting enzyme inhibitory peptides have simple structure, small molecular weight and good angiotensin converting enzyme inhibitory activity, and can be applied to medicaments and functional foods related to blood pressure reduction.
Description
Technical Field
The invention belongs to the technical field of bioactive peptides, and particularly relates to a maca protein source bioactive peptide with angiotensin converting enzyme inhibitory activity and application thereof.
Background
Bioactive peptides are a specific class of protein fragments that regulate the function of an organism, but are generally inactive in protein sequences, and require hydrolysis to release peptide fragments therefrom, which are generally short peptides containing 2 to 12 amino acid residues. It has been proved that part of small peptide can enter cells or blood through small peptide transport system or carrier protein, and further exert physiological activity such as promoting sleep, lowering blood pressure, inhibiting bacteria and reducing blood lipid, so that it can be used in food, health product and medicine production.
Hypertension is one of the important influencing factors which cause multiple chronic patients with cardiovascular and cerebrovascular diseases, although the cause of hypertension is complex, the renin-angiotensin system and kallikrein-kallikrein system in human body play a key role in controlling blood pressure, and angiotensin converting enzyme plays an important role in the two systems, so that the use of angiotensin converting enzyme inhibitors is also a main means for treating hypertension, and the inhibition of angiotensin converting enzyme can inhibit the generation of angiotensin II and promote the release of kallikrein, thereby finally achieving the effect of reducing blood pressure. However, the administration of drugs such as lisinopril, captopril and enalapril may cause adverse reactions such as cough and angioedema to patients with hypertension, while the food-borne angiotensin converting enzyme inhibitory peptide does not have the disadvantages, and has wider sources and higher safety than the traditional antihypertensive drugs.
The protein content in the maca is about 10-18%, the research on the maca protein is still in a starting stage at present, the maca protein has a certain physiological function besides a nutrition function, the maca protein also is a good source for preparing the angiotensin converting enzyme inhibitory peptide, and the research on the maca protein source angiotensin converting enzyme inhibitory peptide has a certain academic significance and is also beneficial to the development and utilization of the maca.
The traditional bioactive peptide screening method has the advantages of multiple steps, long period and low efficiency, takes an angiotensin converting enzyme activity pocket as a target spot, screens angiotensin converting enzyme inhibitory peptide by using on-line analysis tools, molecular docking software and other biological information means, performs in-vitro activity verification, saves a great deal of time, improves screening efficiency, and identifies six new angiotensin converting enzyme inhibitory peptide sequences.
Disclosure of Invention
The invention aims to provide maca protein source active peptide with angiotensin converting enzyme inhibitory activity and application thereof.
The technical scheme of the invention is as follows:
the amino acid sequences of the maca protein source active peptides with angiotensin converting enzyme inhibitory activity are RSRGVFF, LGHPVFRNK, HGSCNYR, KANLGFRF, GGGHKRLY and SSYLGRN respectively.
The active peptide is obtained by screening maca protein.
Preferably, the maca protein source active peptide with the angiotensin converting enzyme inhibitory activity comprises taking the maca protein source active peptide sequence with the angiotensin converting enzyme inhibitory activity as a core, and carrying out any corresponding adjustment or modification on the maca protein source active peptide.
Preferably, the RSRGVFF, LGHPVFRNK, HGSCNYR, KANLGFRF, GGGHKRLY and SSYLGRN pair angiotensin converting enzyme IC 50 The values were 5.01, 8.93, 30.02, 48.75, 138.97 and 140.89. Mu.M, respectively.
Preferably, the maca protein source active peptide with the angiotensin converting enzyme inhibitory activity is derived from maca extraction or artificial synthesis.
Further preferably, the specific preparation method of the maca protein source active peptide through maca extraction comprises the following steps:
(1) Heating and extracting maca powder in an alkaline solution, centrifuging and collecting supernatant, regulating pH of the supernatant to be acidic, centrifuging and collecting precipitate, dialyzing, and drying to obtain maca crude protein;
(2) And (3) carrying out enzymolysis, dialysis and purification on the maca crude protein to obtain the maca protein source active peptide with the angiotensin converting enzyme inhibitory activity.
More preferably, the dialysis of step (1) has a molecular weight cut-off of 3000-4000Da.
More preferably, the enzymolysis in the step (2) is enzymolysis by pepsin and trypsin in sequence.
The maca protein source active peptide with the angiotensin converting enzyme inhibitory activity is applied to the preparation of ACE inhibitors, antihypertensive drugs or antihypertensive health care products.
An ACE inhibitor comprising the above maca protein source active peptide having angiotensin converting enzyme inhibitory activity or a pharmaceutically acceptable salt thereof, or further comprising a pharmaceutically acceptable carrier.
A blood pressure lowering medicine contains maca protein source active peptide with angiotensin converting enzyme inhibitory activity or pharmaceutically acceptable salt thereof, or further comprises a pharmaceutically acceptable carrier.
A blood pressure lowering health product contains maca protein source active peptide with angiotensin converting enzyme inhibitory activity or pharmaceutically acceptable salt thereof, or further comprises a pharmaceutically acceptable carrier.
The invention utilizes an online bioactive peptide database to carry out multiple rounds of virtual screening according to the properties of polypeptide such as molecular weight, bioactivity score, water solubility score, ADMET (absorption, metabolism and toxicity) and the like, obtains six polypeptides stably combined with angiotensin converting enzyme (PDB ID:1O 86) through the butt joint of binding molecules, confirms the in-vitro ACE inhibition activity through high performance liquid chromatography, and simultaneously determines IC 50 Values and suppression types. The amino acid sequences of the six polypeptides are RSRGVFF, LGHPVFRNK, HGSCNYR, KANLGFRF, GGGHKRLY and SSYLGRN, IC, respectively 50 The values were 5.01, 8.93, 30.02, 48.75, 138.97 and 140.89. Mu.M, respectively. Finally, molecular docking software is used to elucidate the interaction site between the polypeptide and the angiotensin converting enzyme.
The six maca protein source active peptides with the angiotensin converting enzyme inhibitory activity provided by the invention have the advantages that RSRGVFF (0.01, 0.005 and 0 mg/mL) is intersected in the third quadrant by a Lineweaver-Burk curve for inhibiting the catalytic reaction of the angiotensin converting enzyme, and the inhibition effect on the angiotensin converting enzyme is shown as a mixed inhibition effect of anti-competition and non-competition; LGHPVFRNK (0.01, 0.005, 0 mg/mL) the linehaver-Burk curves for inhibition of the angiotensin converting enzyme catalytic reaction intersect on the y-axis, and the inhibition of the angiotensin converting enzyme appears to be competitive; HGSCNYR (0.1, 0.05, 0 mg/mL) has a Lineweaver-Burk curve intersecting the y-axis for inhibiting the angiotensin converting enzyme catalytic reaction, and the inhibition of the angiotensin converting enzyme is shown as competitive inhibition; the linehaver-Burk curves of KANLGFRF (0.1, 0.05, 0 mg/mL) inhibiting the angiotensin converting enzyme catalytic reaction intersect on the y-axis, and the inhibition of angiotensin converting enzyme appears to be competitive inhibition.
The polypeptide RSRGVFF of the invention interacts with the following amino acid residues of an active site of angiotensin converting enzyme (PDB ID:1O 86): ala354, glu384, tyr523, gln281, his353, lys511, glu162 and His383, while also interacting with the zinc ion of the catalytic site; the polypeptide LGHPVFRNK interacts with the following amino acid residues of the active site of angiotensin converting enzyme (PDB ID:1O 86): ala354, glu384, tyr523, gln281, his353, lys511, his513, tyr520 and Glu162, while also interacting with the zinc ion of the catalytic site; the polypeptide HGSCNYR interacts with the following amino acid residues at the active site of angiotensin converting enzyme (PDB ID:1O 86): ala354, glu384, tyr523, gln281, his353, lys511, his513, tyr520 and Glu162, while also interacting with the zinc ion of the catalytic site; the polypeptide kangfrf interacts with the following amino acid residues of the active site of angiotensin converting enzyme (PDB ID:1O 86): ala354, glu384, tyr523, gln281, his353, tyr520 and Glu162, while also interacting with the zinc ion of the catalytic site; the polypeptide GGGHKLY interacts with the following amino acid residues of the active site of angiotensin converting enzyme (PDB ID:1O 86): ala354, glu384, tyr523, gln281, his353 and Glu162, while also interacting with the zinc ion of the catalytic site; the polypeptide SSYLGRN interacts with the following amino acid residues at the active site of angiotensin converting enzyme (PDB ID:1O 86): ala354, glu384, tyr523, his353, lys511, his513, tyr520 and Glu162, while also interacting with the zinc ion of the catalytic site.
The beneficial effects of the invention are as follows:
the invention provides six kinds ofThe maca protein source angiotensin converting enzyme inhibitory peptide has good in-vitro angiotensin converting enzyme inhibitory activity and IC 50 The values are 5.01, 8.93, 30.02, 48.75, 138.97 and 140.89 mu M respectively, can be applied to the development of medicines and health care products related to hypertension treatment, and is favorable for the development and utilization of maca.
The six maca protein source angiotensin converting enzyme inhibitory peptides provided by the invention can be obtained through a chemical synthesis method according to the amino acid sequence.
Drawings
FIG. 1 shows the inhibition rate of angiotensin converting enzyme and IC 50 A measurement result diagram;
FIG. 2 is a graph of the Lineweaver-Burk curve of RSRGVFF inhibiting the angiotensin converting enzyme catalytic reaction;
FIG. 3 is a graph of a Lineweaver-Burk curve for LGHPVFRNK inhibiting the angiotensin converting enzyme catalytic reaction;
FIG. 4 is a graph of Lineweaver-Burk for HGSCNYR inhibiting the angiotensin converting enzyme catalytic reaction;
FIG. 5 is a graph of the Lineweaver-Burk plot of KANLGFRF inhibiting angiotensin converting enzyme catalyzed reactions;
FIG. 6 is a 2D plan view of the interaction force of RSRGVFF with angiotensin converting enzyme;
FIG. 7 is a 2D plan view of the interaction force of LGHPVFRNK with angiotensin converting enzyme;
FIG. 8 is a 2D plan view of the interaction force of HGSCNYR and angiotensin converting enzyme;
FIG. 9 is a 2D plan view of the interaction force of KANLGFRF with angiotensin converting enzyme;
FIG. 10 is a 2D plan view of the interaction force between GGGHKLY and angiotensin converting enzyme;
FIG. 11 is a 2D plan view of the interaction force of SSYLGRN with angiotensin converting enzyme.
Detailed Description
In order to better illustrate the present invention, embodiments of the present invention will be further described with reference to the accompanying drawings, but it should be noted that the embodiments do not limit the scope of the present invention, and reference may be made to conventional techniques for process parameters that are not specifically noted.
Example 1
Maca protein extraction
Grinding dry maca into powder, weighing a certain weight of sample, adding the sample into 30 times of Tris buffer (C=0.07 mol/L, pH=10), extracting the solution for 30min in a water bath at 60 ℃, centrifuging the solution for 15min at 4 ℃ and 8000 Xg, and collecting supernatant; then adjusting the pH of the supernatant to 3.75 by using 1mol/L HCl, standing the supernatant at 4 ℃ for 12 hours, centrifuging at 4 ℃ and 8000 Xg for 15 minutes, collecting precipitate, dialyzing the precipitate by using a dialysis bag with the molecular weight of 3500Da (Mw), and freeze-drying the precipitate to obtain maca crude protein, wherein the protein content of the maca crude protein is 87.02 percent by using a Kjeldahl nitrogen determination method.
Example 2
Preparation of maca protein hydrolysate and polypeptide sequence identification
Weighing a certain weight of maca crude protein, preparing a 3.3% protein solution by using distilled water, and heating in a boiling water bath for 30 minutes; cooling to 37deg.C, adjusting pH to 2.0 with 1M HCl solution, adding 4% pepsin, and performing enzymolysis at 37deg.C for 2 hr; then adjusting the pH to 7.5 by using 0.5M NaOH solution, adding 4% trypsin, and carrying out enzymolysis for 2 hours at 37 ℃; after the reaction, heating the mixed solution (95 ℃ for 10 min) to inactivate protease, centrifuging at 4 ℃ and 8000 Xg for 10min, collecting supernatant, dialyzing with dialysis bag with molecular weight of 100Da (Mw) to remove salt, and freeze drying to obtain maca protein hydrolysate; and (3) carrying out sequence identification on the polypeptide in the maca protein hydrolysate by adopting ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
Example 3
Virtual screening and molecular docking of polypeptides
Predicting the bioactivity of the identified maca polypeptide sequence through a PeptideRanker (http:// distilldeep. Ucd. Ie/PeptideRanker /), calculating a score based on a novel N-TO-1 neural network, setting the probability score of the bioactivity from the lowest TO the highest TO be 0-1, setting the threshold TO be 0.5, and selecting the polypeptide sequence with the score of 0.5 or more for the next screening, wherein the polypeptide sequence with the score of 0.5 or more can be considered TO have potential bioactivity; then, predicting the water solubility of the polypeptide based on isoelectric points of the polypeptide, the number of charged residues and the length of the polypeptide by Innovagen (http:// www.innovagen.com/proteomics-tools), and selecting the polypeptide with good water solubility for further screening; ADMET (absorption, metabolism and toxicity) properties of the polypeptides were predicted using admetSAR2 (http:// lmmd.ecl.cn/admetSAR 2), and polypeptides predicted to be HIA+ and BBB+ were considered to have good gastrointestinal absorption and blood brain barrier permeability, and subjected to the next molecular docking experiment.
Angiotensin converting enzyme (PDB ID:1O 86) was interfaced with the polypeptide molecule using AutoDock Vina software, the polypeptide molecule was optimized with MMFF94 force field, and the atomic modification, charge calculation, nonpolar hydrogen incorporation and rotatable bond definition of the polypeptide ligand molecule were performed using AutoDockTools-1.5.7 software. The butt joint center is set as follows: x=40.935, y=32.383, z=47.285, grid box size was set to 20, exhaustiveness was set to 10, and each ligand molecule was docked five times with the same parameters, taking the average of docking binding energies as a screening standard. According to the molecular docking results, six polypeptide sequences, RSRGVFF (Arg Ser Arg Gly Val Phe Phe), LGHPVFRNK (Leu Gly His Pro Val Phe Arg Asn Lys), HGSCNYR (His Gly Ser Cys Asn Tyr Arg), KANLGFRF (Lys Ala Asn Leu Gly Phe Arg Phe), GGGHKRLY (Gly Gly Gly His Lys Arg Leu Tyr) and SSYLGRN (Ser Ser Tyr Leu Gly Arg Asn) respectively, were selected, and the average docking binding energy with angiotensin converting enzyme was-9.90, -9.45, -9.13, -9.85, -9.10 and-9.05 kcal/mol respectively, and these six polypeptides were synthesized by solid phase synthesis for in vitro activity verification.
Example 4
In vitro Activity verification
Verifying the angiotensin converting enzyme inhibitory activity of the polypeptide by high performance liquid chromatography (hippuric acid method), preparing a solution with corresponding concentration, adding 10 μl of angiotensin converting enzyme (0.1U/mL) and 10 μl of polypeptide solution (1 mg/mL) into a sample tube, incubating at 37deg.C for 5min, adding 25 μl of hippuric-histamine-leucine (6.5 mmol.L) -1 ) After 60min of reaction at 37℃80. Mu.L HCl (1 mol) was addedL) terminate the reaction, replace the inhibitor with 10. Mu.L buffer for control tube, replace the inhibitor with 10. Mu.L buffer for blank tube and add 80. Mu.L HCl (1 mol/L) to inactivate the enzyme prior to incubation; after the reaction, the obtained reaction solution was filtered with a 0.22 μm filter membrane, and then the hippuric acid in the sample was quantitatively analyzed by reverse high performance liquid chromatography.
Chromatographic conditions: mobile phase 25% acetonitrile (containing 0.05% TFA); flow rate 0.4 mL/min -1 The method comprises the steps of carrying out a first treatment on the surface of the The detection wavelength is 228nm; the sample injection amount was 20. Mu.L.
The angiotensin converting enzyme inhibition rate was calculated as follows:
wherein: r: ACEI inhibition (%) of ACE; a: peak area of hippuric acid in control group; b: peak area of hippuric acid in experimental group; a is that 0 : peak area of hippuric acid in the blank group.
IC 50 Is defined by: the concentration of inhibitor required to inhibit ACE enzyme activity to half under certain conditions was calculated using buffer formulations as sample solutions of varying concentrations.
The experimental results of in vitro activity verification are shown in figure 1, and the angiotensin converting enzyme inhibition rate of positive control drug Captopril (Captopril) is 96.71%, and the angiotensin converting enzyme inhibition rate of maca protein hydrolysate (MCPH) is 67.76%. Six maca protein source angiotensin converting enzyme inhibitory peptides RSRGVFF, LGHPVFRNK, HGSCNYR, KANLGFRF, GGGHKRLY and SSYLGRN have good angiotensin converting enzyme inhibitory activity, and at the concentration of 1mg/mL, the inhibition rates of the six maca protein source angiotensin converting enzyme inhibitory peptides on the angiotensin converting enzyme activity are 92.04%, 88.34%, 87.93%, 77.87%, 73.11% and 65.91%, respectively. The IC is obtained by measuring the inhibition rate of polypeptides with different concentrations to the activity of angiotensin converting enzyme and calculating 50 The values were 5.01, 8.93, 30.02, 48.75, 138.97 and 140.89. Mu.M, respectively.
Example 5
Analysis of inhibition kinetics of polypeptides on angiotensin converting enzyme
Polypeptide RSRGVFF, LGHPVFRNK, HGSCNYR and kangfrf having high inhibitory activity were analyzed. Preparing the above angiotensin-converting enzyme inhibitory peptide into solutions with different concentrations, respectively measuring inhibitory activity with different concentrations of hippocampal-histamine-leucine solutions (0.65,1.3,3.25 and 6.5 mM) as substrate, quantitatively analyzing hippuric acid in the sample by reverse high performance liquid chromatography, calculating reaction rate, and drawing a Lineweaver-Burk curve by double reciprocal form of Mi equation according to slope K m /V max And intercept 1/V max Determining the inhibition pattern of the angiotensin converting enzyme inhibitory peptide. The linehaver-Burk curve equation is as follows:
the results of the experiment of the inhibition kinetics of the angiotensin converting enzyme by the polypeptide are shown in FIGS. 2 to 5. FIG. 2 is a linehaver-Burk plot of inhibition of the angiotensin converting enzyme catalytic reaction at various concentrations of RSRGVFF (0.01, 0.005, 0 mg/mL), where three straight lines are observed to intersect in the third quadrant, demonstrating that the inhibition of angiotensin converting enzyme by RSRGVFF is manifested as a mixed anti-competitive and non-competitive inhibition; FIG. 3 is a linehaver-Burk plot of inhibition of the angiotensin converting enzyme catalytic reaction at various concentrations LGHPVFRNK (0.01, 0.005, 0 mg/mL) with three straight lines intersecting the y-axis, demonstrating that LGHPVFRNK inhibits angiotensin converting enzyme as a competitive inhibition; FIG. 4 is a Lineweaver-Burk plot of inhibition of the angiotensin converting enzyme catalytic reaction at various concentrations of HGSCNYR (0.1, 0.05, 0 mg/mL), where three straight lines intersecting the y-axis are observed, demonstrating that the inhibition of angiotensin converting enzyme by HGSCNYR is indicative of competitive inhibition; FIG. 5 is a linehaver-Burk plot of inhibition of the angiotensin converting enzyme catalytic reaction at various concentrations of KANLGFRF (0.1, 0.05, 0 mg/mL), where three straight lines are observed intersecting the y-axis, demonstrating that KANLGFRF inhibits angiotensin converting enzyme as a competitive inhibition.
Example 6
Molecular docking analysis of polypeptides and angiotensin converting enzymes
After molecular docking of angiotensin converting enzyme (PDB ID:1O 86) with the polypeptide using AutoDock Vina software, a molecular docking diagram was drawn using Pymol and LigPlot to elucidate the forces between the polypeptide and the angiotensin converting enzyme. FIGS. 6 to 11 show interactions between polypeptides and angiotensin converting enzymes, including hydrogen bonding, hydrophobic interactions, metal complexation, and the like. RSRGVFF interacts with the following amino acid residues of the angiotensin converting enzyme active site: ala354, glu384, tyr523, gln281, his353, lys511, glu162 and His383, while also interacting with the zinc ion of the catalytic site; LGHPVFRNK interacts with the following amino acid residues of the angiotensin converting enzyme active site: ala354, glu384, tyr523, gln281, his353, lys511, his513, tyr520 and Glu162, while also interacting with the zinc ion of the catalytic site; HGSCNYR interacts with the following amino acid residues of the angiotensin converting enzyme active site: ala354, glu384, tyr523, gln281, his353, lys511, his513, tyr520 and Glu162, while also interacting with the zinc ion of the catalytic site; kangfrf interacts with the following amino acid residues of the angiotensin converting enzyme active site: ala354, glu384, tyr523, gln281, his353, tyr520 and Glu162, while also interacting with the zinc ion of the catalytic site; GGGHKLY interacts with the following amino acid residues of the angiotensin converting enzyme active site: ala354, glu384, tyr523, gln281, his353 and Glu162, while also interacting with the zinc ion of the catalytic site; SSYLGRN interacts with the following amino acid residues of the angiotensin converting enzyme active site: ala354, glu384, tyr523, his353, lys511, his513, tyr520 and Glu162, while also interacting with the zinc ion of the catalytic site.
The above results indicate that: the maca protein source angiotensin converting enzyme inhibitory peptide has good inhibitory activity on angiotensin converting enzyme, and can be applied to development of medicines and health-care products related to hypertension treatment.
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.
Claims (10)
1. The maca protein source active peptide with the angiotensin converting enzyme inhibitory activity is characterized in that the amino acid sequences of the maca protein source active peptide with the angiotensin converting enzyme inhibitory activity are RSRGVFF, LGHPVFRNK, HGSCNYR, KANLGFRF, GGGHKRLY and SSYLGRN respectively.
2. The active peptide of maca protein source with angiotensin converting enzyme inhibitory activity of claim 1, comprising any corresponding adjustment or modification thereof with the active peptide sequence of maca protein source with angiotensin converting enzyme inhibitory activity as a core.
3. The maca protein source active peptide with angiotensin converting enzyme inhibitory activity of claim 1, wherein said RSRGVFF, LGHPVFRNK, HGSCNYR, KANLGFRF, GGGHKRLY and SSYLGRN pair angiotensin converting enzyme IC 50 The values were 5.01, 8.93, 30.02, 48.75, 138.97 and 140.89. Mu.M, respectively.
4. The active peptide of maca protein source with angiotensin converting enzyme inhibitory activity of claim 1, wherein said active peptide of maca protein source with angiotensin converting enzyme inhibitory activity is derived from maca extraction or artificial synthesis.
5. The maca protein source active peptide with angiotensin converting enzyme inhibitory activity of claim 4, wherein the specific preparation method of maca protein source active peptide by maca extraction is as follows:
(1) Heating and extracting maca powder in an alkaline solution, centrifuging and collecting supernatant, regulating pH of the supernatant to be acidic, centrifuging and collecting precipitate, dialyzing, and drying to obtain maca crude protein;
(2) And (3) carrying out enzymolysis, dialysis and purification on the maca crude protein to obtain the maca protein source active peptide with the angiotensin converting enzyme inhibitory activity.
6. The active peptide of maca protein source having angiotensin converting enzyme inhibitory activity of claim 5, wherein the dialysis of step (1) has a molecular weight cut-off of 3000-4000Da;
and (2) performing enzymolysis by sequentially using pepsin and trypsin.
7. The use of the maca protein source active peptide with angiotensin converting enzyme inhibitory activity as claimed in claim 1 in the preparation of ACE inhibitors, antihypertensive drugs or antihypertensive health care products.
8. An ACE inhibitor comprising the maca protein source active peptide having angiotensin converting enzyme inhibitory activity of claim 1 or a pharmaceutically acceptable salt thereof, or further comprising a pharmaceutically acceptable carrier.
9. A blood pressure lowering drug comprising the maca protein source active peptide with angiotensin converting enzyme inhibitory activity of claim 1, or a pharmaceutically acceptable salt thereof, or further comprising a pharmaceutically acceptable carrier.
10. A blood pressure lowering health product, characterized by comprising the maca protein source active peptide with angiotensin converting enzyme inhibitory activity or pharmaceutically acceptable salt thereof according to claim 1, or further comprising a pharmaceutically acceptable carrier.
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