CN110540577A - Duck source polypeptide with blood pressure lowering effect and application thereof - Google Patents
Duck source polypeptide with blood pressure lowering effect and application thereof Download PDFInfo
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- CN110540577A CN110540577A CN201910863613.0A CN201910863613A CN110540577A CN 110540577 A CN110540577 A CN 110540577A CN 201910863613 A CN201910863613 A CN 201910863613A CN 110540577 A CN110540577 A CN 110540577A
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- converting enzyme
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 69
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 57
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 56
- 241000272525 Anas platyrhynchos Species 0.000 title claims abstract description 17
- 230000004531 blood pressure lowering effect Effects 0.000 title claims description 5
- 239000005541 ACE inhibitor Substances 0.000 claims abstract description 29
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims abstract description 29
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 25
- 230000036772 blood pressure Effects 0.000 claims abstract description 13
- 230000000694 effects Effects 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 12
- 206010020772 Hypertension Diseases 0.000 claims abstract description 10
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 claims abstract description 9
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 claims abstract description 8
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- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 4
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- 238000004128 high performance liquid chromatography Methods 0.000 description 4
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 4
- 150000001413 amino acids Chemical group 0.000 description 3
- CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 2
- 102400000345 Angiotensin-2 Human genes 0.000 description 2
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- 101800004538 Bradykinin Proteins 0.000 description 2
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- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 2
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- 241000251468 Actinopterygii Species 0.000 description 1
- HUUOZYZWNCXTFK-INTQDDNPSA-N Ala-His-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N2CCC[C@@H]2C(=O)O)N HUUOZYZWNCXTFK-INTQDDNPSA-N 0.000 description 1
- 241000272522 Anas Species 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 244000025361 Ficus carica Species 0.000 description 1
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- DTMLKCYOQKZXKZ-HJGDQZAQSA-N Gln-Arg-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DTMLKCYOQKZXKZ-HJGDQZAQSA-N 0.000 description 1
- 235000006439 Lemna minor Nutrition 0.000 description 1
- 244000242291 Lemna paucicostata Species 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- SCSVNSNWUTYSFO-WDCWCFNPSA-N Thr-Lys-Glu Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O SCSVNSNWUTYSFO-WDCWCFNPSA-N 0.000 description 1
- LGEYOIQBBIPHQN-UWJYBYFXSA-N Tyr-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 LGEYOIQBBIPHQN-UWJYBYFXSA-N 0.000 description 1
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- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 235000013364 duck meat Nutrition 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 235000019688 fish Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
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- 239000003998 snake venom Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 108010031491 threonyl-lysyl-glutamic acid Proteins 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 239000005019 zein Substances 0.000 description 1
- 229940093612 zein Drugs 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- 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
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- 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
-
- 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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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Molecular Biology (AREA)
- Heart & Thoracic Surgery (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Urology & Nephrology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Hospice & Palliative Care (AREA)
- Biochemistry (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides duck source polypeptide with a blood pressure reducing effect and application thereof, and belongs to the technical field of biology. The amino acid sequence of the duck source polypeptide with the blood pressure reducing effect is shown in a sequence table SEQ ID No. 1. The polypeptide has stronger ACE enzyme inhibitory activity, so that the polypeptide can be used as an ACE inhibitor to inhibit the activity of angiotensin converting enzyme, and simultaneously participates in the occurrence and development of various diseases based on the ACE enzyme, so that the duck-origin polypeptide is applied to the preparation of medicines for treating hypertension, cardiovascular diseases, heart failure or renal failure.
Description
Technical Field
The invention belongs to the technical field of biology, and particularly relates to duck source polypeptide with a blood pressure reducing effect and application thereof.
Background
Angiotensin converting enzyme (Angiotensin converting enzyme, ACE, ec3.4.15.1, previously known in the literature as kininasei, dipeptidyl carboxypeptidase I, etc.) is a dicarboxypeptidase, a key enzyme responsible for hypertension, which converts Angiotensin I to Angiotensin ii by hydrolysis. At the same time, ACE inactivates bradykinin, both of which can cause vasoconstriction and thus hypertension. ACE is therefore considered to be an important factor in the development of hypertension. The research shows that an Angiotensin Converting Enzyme Inhibitor (ACEI) can achieve the effect of reducing blood pressure by inhibiting the activity of ACE. ACE inhibitors are widely used for the treatment of cardiovascular, hypertension, heart failure, renal failure, etc. The common blood pressure lowering drugs are urine benefiting agents, tablet receptor blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, a-receptor blockers, angiotensin II receptor antagonists and the like, and the drugs have uneven blood pressure lowering effects.
ACE inhibitors were initially discovered from snake venom, and ACE inhibitory peptides extracted from food materials such as gelatin, casein, fish, ficus carica gum, alpha-zein, and the like were subsequently found to be useful as starting materials for the preparation of ACE inhibitory peptides. Different peptide sequences of potential specific target active peptides are different, and the peptide sequences obtained under the action of the same enzyme or different enzymes are different.
Disclosure of Invention
In view of the above, the present invention aims to provide a duck-origin polypeptide having ACE inhibitory activity and applications thereof.
The invention provides duck source polypeptide with a blood pressure reducing effect, and an amino acid sequence of the duck source polypeptide is shown in a sequence table SEQ ID No. 1.
The invention provides an angiotensin converting enzyme inhibitor, which comprises the duck-origin polypeptide.
The invention provides application of the duck-origin polypeptide or the angiotensin converting enzyme inhibitor in inhibiting the activity of angiotensin converting enzyme.
Preferably, the concentration of the duck-origin polypeptide is more than or equal to 1.0 mg/mL.
preferably, the concentration of the duck-origin polypeptide is 2.0-3.0 mg/mL.
The invention provides application of the duck-origin polypeptide or the angiotensin converting enzyme inhibitor in preparation of a medicine for treating hypertension.
The invention provides application of the duck-origin polypeptide or the angiotensin converting enzyme inhibitor in health care products for reducing blood pressure.
The invention provides application of the duck-origin polypeptide or the angiotensin converting enzyme inhibitor in preparation of a medicine for treating cardiovascular diseases, heart failure diseases or renal failure diseases.
The invention provides duck source polypeptide with a blood pressure reducing effect, and an amino acid sequence of the duck source polypeptide is shown in a sequence table SEQ ID No. 1. The polypeptide is a 12 peptide sequence and has inhibitory activity against ACE targets. According to the results of ACE inhibitory activity experiments, the ACE inhibitory activity at 1.0mg/mL is 78.16%, and the ACE inhibitory activity at 2.0mg/mL is 86.13%, which shows that the polypeptide provided by the invention has strong ACE enzyme inhibitory activity.
Detailed Description
The invention provides duck-origin polypeptide with a blood pressure reducing effect, wherein the amino acid sequence of the duck-origin polypeptide is shown as a sequence table SEQ ID No.1 (Gln-Arg-Thr-Tyr-Ala-Ser-Thr-Lys-Glu-Ala-His-Pro). The polypeptide is derived from Chinese duck (NCBI Reference Sequence: NP-001297320.1, Molecular cloning of the fatty acid gene and its association with cars and fats in Chinese ducks. Gene. mol. Res.2013,12(2),1582 and 1592) protein, and the gene expressing the protein has correlation with the quality of duck meat. The ACE inhibitory peptide obtained under the action condition of pepsin (pH is less than or equal to 1.3) is obtained by a computer-assisted virtual enzymolysis technology. Experiments prove that the duck-origin polypeptide has strong angiotensin converting enzyme inhibitory activity, the angiotensin converting enzyme is a key enzyme for causing hypertension, angiotensin I is converted into angiotensin II through hydrolysis, ACE can also inactivate bradykinin, the two effects can cause vasoconstriction to cause hypertension, and the duck-origin polypeptide has the effect of reducing the blood pressure through inhibiting the ACE activity. The source of the duck source polypeptide is not particularly limited, and a polypeptide synthesis method common in the field is adopted. In the examples of the present invention, the duck-derived polypeptide was synthesized by Jier Biochemical (Shanghai) Co., Ltd.
The invention provides an angiotensin converting enzyme inhibitor, which comprises the duck-origin polypeptide. The weight percentage of the duck-origin polypeptide is preferably 80-90%. The angiotensin converting enzyme inhibitor preferably also comprises auxiliary materials acceptable in the field of inhibitors. The method for producing the angiotensin converting enzyme inhibitor of the present invention is not particularly limited, and a method for producing an enzyme inhibitor known in the art may be used.
Based on the fact that the duck-origin polypeptide has strong ACE enzyme inhibitory activity, the invention provides application of the duck-origin polypeptide or the angiotensin converting enzyme inhibitor in inhibition of angiotensin converting enzyme activity. In the invention, the concentration of the duck-origin polypeptide is preferably not less than 1.0mg/mL, and more preferably 2.0-3.0 mg/mL. The solvent for dissolving the duck-origin polypeptide is preferably 0.1moL/L boric acid buffer solution containing 0.3moL/L NaCl and having a pH value of 8.3.
The invention provides application of the duck-origin polypeptide or the angiotensin converting enzyme inhibitor in preparation of a medicine for treating hypertension, wherein the duck-origin polypeptide or the angiotensin converting enzyme inhibitor has strong ACE enzyme inhibition activity. The invention provides application of the duck-origin polypeptide or the angiotensin converting enzyme inhibitor in health care products for reducing blood pressure.
Based on the fact that ACE inhibitors are also widely used for treating cardiovascular diseases, heart failure, renal failure and other diseases, the invention provides application of the duck-origin polypeptide or the angiotensin converting enzyme inhibitor in preparation of medicines for treating cardiovascular diseases, heart failure diseases or renal failure diseases.
In the invention, the dosage form of the medicine prepared from the duck-origin polypeptide is preferably oral preparation. In the medicine, the concentration of the duck-origin polypeptide is 1.0-2.0 mg/mL, and more preferably 2.0 mg/mL. The preferable taking method of the medicine is 2g per time and 2-3 times per day.
The duck-origin polypeptide having the function of lowering blood pressure and the application thereof provided by the present invention will be described in detail with reference to the following examples, which should not be construed as limiting the scope of the present invention.
Example 1
Method for detecting ACE inhibitory activity
ACE catalyzes and decomposes a mimic of angiotensin I, Hippuryl-L-Histidyl-L-Leucine (HHL) to generate Hippuric Acid (HA) at 37 ℃ and pH value of 8.3, wherein the substance HAs a characteristic absorption peak at 225nm in ultraviolet; when an ACE inhibitor is added, the catalytic decomposition of HHL by ACE is inhibited, the amount of hippuric acid produced is reduced, and the change of the amount of hippuric acid produced before and after the inhibitor is added is measured by HPLC method to calculate the inhibiting activity.
The reaction system is as follows: mu.L of 0.1U/mL ACE and 50. mu.L of 1.0mg/mLACE inhibitory peptide solution are added in sequence, the mixture is incubated at 37 ℃ for 5min, 10. mu.L of 5mM HHL substrate is added to start the catalytic reaction of the ACE, and 250. mu.L of 1.0moL/L HCl is added to stop the reaction after shaking the water bath at 37 ℃ for 30 min. The system solution passes through a filter membrane of 0.45 mu m and then is subjected to RP-HPLC detection to analyze the content of Hippuric Acid (HA). Under the same conditions as above, 50. mu.L of 0.1moL/L boric acid buffer (containing 0.3moL/L NaCl, pH 8.3) was used as a blank reaction system in place of ACE inhibitor. The ACE and HHL substrates are both prepared by using 0.1moL/L boric acid buffer (containing 0.3moL/L NaCl, pH 8.3) as solvent. ACE inhibitory peptide (KDTISTP) was dissolved in 0.1moL/L boric acid buffer (containing 0.3moL/L NaCl, pH 8.3) to give an ACE inhibitory peptide solution.
HPLC chromatographic conditions: solvent I was 0.05% trifluoroacetic acid (TFA) and 0.05% triethylamine (TTA) in deionized water (i.e., 0.5mL trifluoroacetic acid and 0.5mL triethylamine per liter of solvent I) and solvent II was 100% chromatographically pure acetonitrile. The proportion of the solvent I to the solvent II is 70%: 30 percent (volume ratio), an ultimate3000 dean liquid chromatograph, a water Symmetry C185 mu m4.6 multiplied by 250mm chromatographic column, a flow rate of 0.5mL/min, a sample injection amount of 10 mu L, a detection wavelength of 225nm and a detection column temperature of 30 ℃.
And (3) RP-HPLC detection: solvent I was 0.05% (V/V) trifluoroacetic acid (TFA) and 0.05% (V/V) triethylamine (TTA) in deionized water, and solvent II was 100% chromatographically pure acetonitrile. The proportion of the solvent I to the solvent II is 70%: 30 percent (volume ratio), the flow rate is 0.5mL/min, the detection wavelength is 225nm, and the detection column temperature is 30 ℃.
ACE inhibitory activity was calculated according to the following formula:
I％＝(A-B)/A×100％
A: peak area of hippuric acid without addition of a short peptide inhibitor;
B: peak area of hippuric acid when adding short peptide inhibitor;
ACE: the 1U unit is defined as the amount of ACE consumed in the production of 1. mu.M hippuric acid by catalyzing the substrate (HHL) at 37 ℃ over a period of 1min under standard assay conditions. I.e. the activity unit of ACE.
As a result: the ACE inhibitory activity of peptide KDTISTP at 1.0mg/mL was 78.16%.
example 2
Method for detecting ACE inhibitory activity
ACE catalyzes and decomposes a mimic of angiotensin I, Hippuryl-L-Histidyl-L-Leucine (HHL) to generate Hippuric Acid (HA) at 37 ℃ and pH value of 8.3, wherein the substance HAs a characteristic absorption peak at 225nm in ultraviolet; when an ACE inhibitor is added, the catalytic decomposition of HHL by ACE is inhibited, the amount of hippuric acid produced is reduced, and the change of the amount of hippuric acid produced before and after the inhibitor is added is measured by HPLC method to calculate the inhibiting activity.
The reaction system is as follows: mu.L of 0.1U/mL ACE and 50. mu.L of 2.0mg/mLACE inhibitory peptide solution are added in sequence, the mixture is incubated at 37 ℃ for 5min, 10. mu.L of 5mM HHL substrate is added to start the catalytic reaction of the ACE, and 250. mu.L of 1.0moL/L HCl is added to stop the reaction after shaking the water bath at 37 ℃ for 30 min. The system solution passes through a filter membrane of 0.45 mu m and then is subjected to RP-HPLC detection to analyze the content of Hippuric Acid (HA). Under the same conditions as above, 50. mu.L of 0.1moL/L boric acid buffer (containing 0.3moL/L NaCl, pH 8.3) was used as a blank reaction system in place of ACE inhibitor. The ACE and HHL substrates are both prepared by using 0.1moL/L boric acid buffer (containing 0.3moL/L NaCl, pH 8.3) as solvent. ACE inhibitory peptide (KDTISTP) was dissolved in 0.1moL/L boric acid buffer (containing 0.3moL/L NaCl, pH 8.3) to give an ACE inhibitory peptide solution.
HPLC chromatographic conditions: solvent I was 0.05% trifluoroacetic acid (TFA) and 0.05% triethylamine (TTA) in deionized water (i.e., 0.5mL trifluoroacetic acid and 0.5mL triethylamine per liter of solvent I) and solvent II was 100% chromatographically pure acetonitrile. The proportion of the solvent I to the solvent II is 70%: 30 percent (volume ratio), an ultimate3000 dean liquid chromatograph, a water Symmetry C185 mu m4.6 multiplied by 250mm chromatographic column, a flow rate of 0.5mL/min, a sample injection amount of 10 mu L, a detection wavelength of 225nm and a detection column temperature of 30 ℃.
And (3) RP-HPLC detection: solvent I was 0.05% (V/V) trifluoroacetic acid (TFA) and 0.05% (V/V) triethylamine (TTA) in deionized water, and solvent II was 100% chromatographically pure acetonitrile. The proportion of the solvent I to the solvent II is 70%: 30 percent (volume ratio), the flow rate is 0.5mL/min, the detection wavelength is 225nm, and the detection column temperature is 30 ℃.
ACE inhibitory activity was calculated according to the following formula:
I％＝(A-B)/A×100％
A: peak area of hippuric acid without addition of a short peptide inhibitor;
B: peak area of hippuric acid when adding short peptide inhibitor;
ACE: the 1U unit is defined as the amount of ACE consumed in the production of 1. mu.M hippuric acid by catalyzing the substrate (HHL) at 37 ℃ over a period of 1min under standard assay conditions. I.e. the activity unit of ACE.
As a result: the ACE inhibitory activity of peptide KDTISTP at 1.0mg/mL was 86.13%.
According to the embodiment, the activity and concentration of the duck source polypeptide sequence have a dose-effect relationship, the polypeptide has ACE inhibitory activity which is not reported, and the duck source polypeptide belongs to a novel functional peptide with ACE inhibitory activity.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Sequence listing
<110> Zhejiang province academy of agricultural sciences
<120> duck source polypeptide with blood pressure lowering effect and application thereof
<160> 1
<170> SIPOSequenceListing 1.0
<210> 1
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 1
Gln Arg Thr Tyr Ala Ser Thr Lys Glu Ala His Pro
1 5 10
Claims (8)
1. The duck-origin polypeptide with the blood pressure lowering effect is characterized in that the amino acid sequence of the duck-origin polypeptide is shown in a sequence table SEQ ID No. 1.
2. an angiotensin converting enzyme inhibitor comprising the duck-origin polypeptide of claim 1.
3. use of the duck-derived polypeptide of claim 1 or the angiotensin-converting enzyme inhibitor of claim 2 for inhibiting angiotensin-converting enzyme activity.
4. The use of claim 3, wherein the concentration of said duck-derived polypeptide is greater than or equal to 1.0 mg/mL.
5. The use of claim 3, wherein the concentration of the duck-origin polypeptide is 2.0-3.0 mg/mL.
6. Use of the duck-origin polypeptide of claim 1 or the angiotensin-converting enzyme inhibitor of claim 2 for the preparation of a medicament for the treatment of hypertension.
7. Use of the duck-origin polypeptide of claim 1 or the angiotensin-converting enzyme inhibitor of claim 2 in a health product for lowering blood pressure.
8. Use of the duck-origin polypeptide of claim 1 or the angiotensin-converting enzyme inhibitor of claim 2 for the manufacture of a medicament for the treatment of cardiovascular disease, heart failure disease or renal failure disease.
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| CN110563803A (en) * | 2019-09-12 | 2019-12-13 | 浙江省农业科学院 | Duck-origin polypeptide with angiotensin converting enzyme inhibitory activity and application thereof |
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