CN107312064A - A kind of antihypertensive active peptide GABA The Pro and application and pharmaceutical composition - Google Patents
A kind of antihypertensive active peptide GABA The Pro and application and pharmaceutical composition Download PDFInfo
- Publication number
- CN107312064A CN107312064A CN201710619459.3A CN201710619459A CN107312064A CN 107312064 A CN107312064 A CN 107312064A CN 201710619459 A CN201710619459 A CN 201710619459A CN 107312064 A CN107312064 A CN 107312064A
- Authority
- CN
- China
- Prior art keywords
- pro
- active peptide
- gaba
- antihypertensive
- pharmaceutical composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0205—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Abstract
The present invention relates to a kind of antihypertensive active peptide GABA The Pro and application and pharmaceutical composition.The amino acid sequence of the active peptide is：γ aminobutyryl tea aminoacyl proline, with structure shown in Formulas I.The present invention proposes a kind of new active peptide, the IC50 of Angiotensin-Converting (ACE) activity suppression of the active peptide is 207.64 μm of ol/L, minimum point 166mmHg is dropped to from 187mmHg using blood pressure after congenital Hypertensive Rats of the dosage gavage of 1.5mg/kg body weight 2.5 hours, the constant drug effect time is 3.5 hours.
Description
Technical field
The invention belongs to biomedicine field, more particularly, to a kind of antihypertensive active peptide GABA-The-Pro and
Using, and a kind of antihypertensive pharmaceutical composition.
Background technology
《Chinese cardiovascular disease report 2015》Point out that the ill rate of cardiovascular disease of China is in and continue ascent stage.Hypertension
Be angiocardiopathy Major Risk Factors into common recognition, it be the promotion that persistently rises of China's angiocardiopathy illness rate because
Element.Ministry of Public Health's statistics in 2014 shows that the hypertension sufferer rate of China is 25.5%, and some provinces reach 27.9%, the whole nation
Hyperpietic's number is estimated up to 2.7 hundred million.
At present, many drugs for hypertension are considered as the medicine of a clinical line, wherein Angiotensin-Converting
Inhibitor (ACEI) is the best medicine of clinical effectiveness, and how general such as enalapril, captopril, Benazepril, lisinopril, group be
Profit etc..But they still have certain side effect, such as dry cough, fash, angioedema and injury of kidney.
ACEI class medicines are a class peptides and modified amino acid class material, and natural albumen is abundant peptide resource.Cause
This, scientists are endeavoured to prepare ACEI active peptides by the way of enzyme hydrolysis and fermentation always, to make hyperpietic
Benefit.As two with anti-hypertension bioactivity tripeptides " VPP " (Val-Pro-Pro, VPP) and " IPP " (Ile-Pro-
Pro, IPP) it is accredited out.But, high, the repeated low, bioavailability of this preparation method cost is low, in the urgent need to development
A kind of new replacement production technology.These researchs are all based on the peptide information contained in protein, although with peptide molecular weight
Increase, its structure will vary, and activity will also have potentiality further, but be due to the molecular sieving effect and Qi Fu of intestinal mucosa
The peptase contained, constrains and utilizes the active development of resources ACEI peptides small-molecule substances of native protein.Therefore, how chemistry is evaded
The side effect of modification peptides or amino acids ACEI small-molecule drugs and avoid internal peptase hydrolysis and absorbed intact, as opening
The ACEI small-molecule drug study hotspots that hair safety has no side effect.
The content of the invention
It is an object of the invention to provide a kind of antihypertensive active peptide GABA-The-Pro and application and pharmaceutical composition.
The first aspect of the present invention is to provide a kind of antihypertensive active peptide GABA-The-Pro, the amino of the active peptide
Acid sequence is：Gamma-amino butyryl-tea aminoacyl-proline, with structure shown in Formulas I.Referred to as GABA-The-Pro (γ-
aminobutyric acid(GABA)-Theanine(The)-Proline (Pro))。
The active feature request to constituting amino acid residue of the invention according to anti-hypertension ACEI class peptide molecules, i.e., it is quantitative
Feature rare amino acid in structure-activity relationship (QSAR), and common food plant tea, different order is analyzed by molecular docking
Binding ability between the tri-peptide molecule and Angiotensin-Converting (ACE) molecule of amino acid residue combination, primarily determines that tool
There is antihypertensive peptide molecule, prepared by liquid phase synthesizing method, further verified by vitro and in vivo bioactivity, screening is true
The fixed synthetic peptide with stronger antihypertensive active.The antihypertensive active peptide can be made by the conventional method of this area, example
Such as liquid phase synthesizing method.
The second aspect of the present invention provide described antihypertensive active peptide GABA-The-Pro prepare it is antihypertensive
Application in medicine and food.
The third aspect of the present invention provides a kind of antihypertensive pharmaceutical composition, including active ingredient and auxiliary material, described
Active ingredient include described antihypertensive active peptide GABA-The-Pro.
According to the present invention, the auxiliary material can be conventional various pharmaceutic adjuvants or food additives.
The present invention has following advantage compared with prior art：
The present invention proposes a kind of different active peptide.Prior art passes through external proteolysis or micro- from native protein
Biofermentation separation obtains active peptide, can further be hydrolyzed by the peptase being rich in intestinal mucosa, reduces it actual in vivo
Effect.The active peptide of the present invention is made up of rare amino acid and conventional amino acid, in native protein and in the absence of such sequence
Row are constituted.Therefore, active peptide of the invention can escape the further hydrolysis of vivo protein enzyme, it is ensured that its integrality absorbed
The stability acted in vivo.
The IC of Angiotensin-Converting (ACE) activity suppression of active peptide of the present invention50For 207.64 μm of ol/L, use
The congenital Hypertensive Rats of dosage gavage of 1.5mg/kg body weight after 2.5 hours blood pressure drop to minimum point from 187mmHg
166mmHg, the constant drug effect time is 3.5 hours.
Other features and advantages of the present invention will be described in detail in subsequent embodiment part.
Brief description of the drawings
By the way that exemplary embodiment of the invention is described in more detail with reference to accompanying drawing, it is of the invention above-mentioned and its
Its purpose, feature and advantage will be apparent.
Fig. 1 is GABA-The-Pro to congenital hypertensive rat blood pressure function analysis laboratory test results figure.
Embodiment
With reference to specific embodiment, the present invention will be further described in detail, but implements the invention is not restricted to following
Example.In following examples, when being not particularly illustrated, " % " refers both to mass percent.
Embodiment 1
The synthesis of GABA-The-Pro tripeptides.Antihypertensive active peptide of the present invention can be synthesized by artificial chemistry, specifically
Operation is as follows：
Polypeptide of the present invention is synthesized using Liquid phase peptides synthesis method, by a certain amount of N- tertbutyloxycarbonyls theanine methyl esters
(Boc-The-OH) inserted with proline methyl ester hydrochloride (H-Pro-Ome.HCl) in round-bottomed flask, add dimethylformamide
(DMF) clarification is dissolved to, N-methyl morpholine (NMM) and dicyclohexylcarbodiimide (DCC) is continuously added, is gently mixed, instead
It should stay overnight.
Further, above-mentioned reaction solution is filtered by vacuum, ethyl acrylate (EA) and H is added in filtrate2O enters
Row chromatography.Supernatant liquid is drawn, using NaHCO3/H2O is washed 2 times, then with citric acid/H2O is washed 2 times, and saturation NaCl solution is washed
Wash 2 times, Na2SO4Dry, the grease that Rotary Evaporators are evaporated acquisition is N- tertbutyloxycarbonyl tea aminoacyl proline methyl esters (Boc-
The-Pro-Ome)。
Further, 4N hydrogen chloride gas/ethyl acrylate, dissolving are added in N- tertbutyloxycarbonyl tea aminoacyl proline methyl esters
To clarifying, reaction 2 hours is stirred at room temperature.Add the absolute ether of 6-8 times of volume while stirring in reaction solution, chromatographed,
4000rpm is centrifuged 3 minutes.Abandon after supernatant and use ether repeated washing 5 times, precipitation obtains white solid matter and be dried in vacuo
To tea aminoacyl proline methyl ester hydrochloride (H-The-Pro-Ome.HCl).
Further, by a certain amount of N- tertbutyloxycarbonyls γ-aminobutyric acid methyl esters (Boc-GABA-OH) and tea aminoacyl
Proline methyl ester hydrochloride (H-The-Pro-Ome.HCl) is inserted in round-bottomed flask, is added dimethylformamide (DMF) and is dissolved to
Clarification, continuously adds N-methyl morpholine (NMM) and dicyclohexylcarbodiimide (DCC), is gently mixed, reaction is stayed overnight.
Further, confirm whether reaction is complete by thin-layer chromatography (TCL).Above-mentioned reaction solution is filtered by vacuum,
Ethyl acrylate (EA) and H are added in filtrate2O is chromatographed.Supernatant liquid is drawn, using NaHCO3/H2O is washed 2 times, then
With citric acid/H2O is washed 2 times, and saturation NaCl solution is washed 2 times, Na2SO4 is dried, and Rotary Evaporators are evaporated the grease of acquisition
For N- tertbutyloxycarbonyl gamma-amino butyryl tea aminoacyl proline methyl esters (Boc-GABA-The-Pro-Ome).
Further, in N- tertbutyloxycarbonyl gamma-amino butyryl tea aminoacyl proline methyl esters (Boc-GABA-The-Pro-
Ome methanol (MeOH) and tetrahydrofuran (THF) (1 are added in):1) solution is stirred reaction, and hydrogen-oxygen is added after solution clarification
Change lithium (LiOH)/H2O regulation pH ≈ 13, are kept for 2 hours, confirm whether reaction is complete by thin-layer chromatography (TCL).By reaction solution
Separatory funnel is inserted, polyethylene terephthalate (PET) cyclic washing is added 2 times, interception lower floor liquid.In lower floor's liquid
Middle addition ethyl acrylate, is adjusted after solution to acidity with 2N HCl, is placed in separatory funnel layering, is passed through thin-layer chromatography (TCL)
Confirm, intercept supernatant liquid.By supernatant liquid citric acid/H2O is washed 2 times, and saturation NaCl solution is washed 2 times, Na2SO4It is dry
Dry, the grease that Rotary Evaporators are evaporated acquisition is N- tertbutyloxycarbonyl gamma-amino butyryl tea aminoacyl proline (Boc-GABA-
The-Pro-OH)。
4N salt is added in N- tertbutyloxycarbonyl gamma-amino butyryl tea aminoacyl proline (Boc-GABA-The-Pro-OH)
Acid gas/ethyl acrylate, is dissolved to clarification, and reaction 2 hours is stirred at room temperature.Add 6-8 times of volume while stirring in reaction solution
Absolute ether, chromatographed, 4000rpm centrifuge 3 minutes.Abandon after supernatant and use ether repeated washing 5 times, it is solid that precipitation obtains white
Body material be dried in vacuo obtaining gamma-amino butyryl tea aminoacyl proline tripeptides (GABA-The-Pro) semifinished product.
Further, semifinished product passes through semi-preparative reverse-phase high performance liquid chromatography (reversed-phase column：30 × 250 millimeters of Yi Lite
C18Post；Mobile phase (acetonitrile of A liquid 100% (ACN), B liquid 100%H2O), linear gradient 14%~80%；The ml/min of flow velocity 3)
Eluting peak is separated and collected, it is standby after freezing.
Embodiment 2
Extracorporeal blood vessel Converting Enzyme (ACE) active suppression test.
Horse urea acyl histidyl- leucine (hippuryl-L-histidyl-L-leucine, HHL) is under the catalysis of ACE enzymes
Fast decoupled produces hippuric acid (Hippuric Acid, HA) and dipeptides histidyl-leucine (HL), adds ACE enzyme levels
After agent, the activity of ACE enzymes is suppressed, and HA and HL growing amount are reduced, and ACE is extracted by rabbit lung in the present embodiment, enzyme activity
For 0.76mU/mL, developed the color by DAB, HA growing amounts are determined using spectrophotometer method, analyze ACE enzyme activity.Ethyl acetate is carried
The hippuric acid in reactant is taken, it is then anti-with the pyridine solution (DAB developers) containing paradime thylaminobenzaldehyde in acetic anhydride
Bisque compound should be generated, directly in its OD value of 459nm colorimetric estimations, ACE enzyme inhibitors pair are evaluated by following equation
The inhibiting rate of ACE enzymes.Concentration (the IC of synthesis tripeptides needed for being suppressed with 50% ACE enzymatic activitys50) define synthesis tripeptides
ACE inhibitory activity.
ACE inhibitory activity (%)=[(ODcontrol-ODsample)/(ODcontrol-ODblank)] × 100%
Specific reaction system and condition are shown in Table 1.
Table 1
The present embodiment method measures the active kyrine of the present invention to ACE inhibitory activity IC50For 207.64 μm of ol/L.
Embodiment 3
The internal drop test of congenital Hypertensive Rats (SHR).
Using the intelligent non-invasive blood pressure instrument of SoftronBP-98A types rat, the systolic pressure for covering tail method measure rat is utilized
(SBP)。
Under SHR rats (spontaneous hypertensive rat) waking state, mouse is placed in mouse bag first, constant temperature is kept,
The method that set tail determines tail vein blood pressure is carried out using the intelligent non-invasive blood pressure instrument of SoftronBP-98A types rat, rat is determined
Systolic pressure (SBP).Start to determine the blood pressure of rat every other day in experiment the last week, experimental record is started after rat stabilization is adapted to.
First determine gavage before rat blood pressure, then 1.5mg/kg body weight doses carry out sample (active kyrine made from embodiment 1,
GABA-The-Pro) gavage, the isometric physiological saline of blank control group gavage (Saline), drug control group gavage 10mg/kg
The drug for hypertension captopril (captopril) of body weight is carried out continuously monitoring of blood pressure 4 hours, every 30 minutes after sample gavage
Continuous record rat blood pressure.Each test point determines the blood pressure of 3 rats, and the interval time determined every time about 1 is analyzed, and takes 3
The average value of secondary measured value as the test point rat blood pressure.
Fig. 1 is after saline control group, drug for hypertension control group and synthesizing activity peptide group rat oral gavage are administered
Blood pressure situation, its data measured carries out system processing with SPSS system softwares, using the t methods of inspection.Can by experimental result
Know, compared with drug control group, the pressure reduction effect of synthetic peptide is more sluggish 30 minutes or so than medicine group, while Effect time is relatively
It is short, about 3.5 hours.Synthesizing activity peptide gavage 2.5 as a child after, SHR blood pressures drop significantly to minimum from initial 187mmHg
Point about 166mmHg, after gavage 4 hours, blood pressure rises to initial pressure value.Illustrate active peptide of the present invention (GABA-The-Pro)
With preferable blood pressure lowering effect.
It is described above various embodiments of the present invention, described above is exemplary, and non-exclusive, and
It is not limited to disclosed each embodiment.In the case of without departing from the scope and spirit of illustrated each embodiment, for this skill
Many modifications and changes will be apparent from for the those of ordinary skill in art field.
Claims (4)
1. a kind of antihypertensive active peptide GABA-The-Pro, it is characterised in that the amino acid sequence of the active peptide is：γ-
Aminobutyryl-tea aminoacyl-proline, with structure shown in Formulas I：
2. the antihypertensive active peptide GABA-The-Pro described in claim 1 is in antihypertensive medicine and food is prepared
Using.
3. a kind of antihypertensive pharmaceutical composition, including active ingredient and auxiliary material, it is characterised in that described active ingredient bag
Include antihypertensive active peptide GABA-The-Pro as claimed in claim 1.
4. pharmaceutical composition according to claim 3, wherein, the auxiliary material is pharmaceutic adjuvant or food additives.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710619459.3A CN107312064A (en) | 2017-07-26 | 2017-07-26 | A kind of antihypertensive active peptide GABA The Pro and application and pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710619459.3A CN107312064A (en) | 2017-07-26 | 2017-07-26 | A kind of antihypertensive active peptide GABA The Pro and application and pharmaceutical composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107312064A true CN107312064A (en) | 2017-11-03 |
Family
ID=60175013
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710619459.3A Pending CN107312064A (en) | 2017-07-26 | 2017-07-26 | A kind of antihypertensive active peptide GABA The Pro and application and pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107312064A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108358998A (en) * | 2018-04-25 | 2018-08-03 | 宁波大学 | A kind of siphon-worm peptide and its application in preparing gestation hypertension medicine |
| CN111848728A (en) * | 2019-04-30 | 2020-10-30 | 首都医科大学 | Preparation, activity and application of theanyl tetrahydroimidazopyridine-6-formyl-L-histidine |
| CN111848724A (en) * | 2019-04-30 | 2020-10-30 | 首都医科大学 | Preparation, activity and application of theanyl tetrahydroimidazopyridine-6-formyl acidic amino acid |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1623600A (en) * | 2003-12-04 | 2005-06-08 | 中国科学院大连化学物理研究所 | Inhibitor of angiotensin I transferase activity and its application |
| CN102399261A (en) * | 2010-09-07 | 2012-04-04 | 任发政 | Tripeptide with angiotensin converting enzyme C-terminal selective inhibition activity, application and composition thereof |
| CN102399262A (en) * | 2010-09-07 | 2012-04-04 | 任发政 | Tripeptides with angiotensin converting enzyme inhibition activity and their use and composition |
| CN104736552A (en) * | 2012-08-24 | 2015-06-24 | 庆熙大学校产学协力团 | Pharmaceutical composition comprising, as active ingredients, peptides which exhibit inhibitory activity against angiotensin-I converting enzyme for preventing or treating cardiovascular diseases |
| CN105001139A (en) * | 2015-07-08 | 2015-10-28 | 南京葆赫生物技术有限公司 | Antihypertensive active peptide, preparation method thereof and application thereof |
| CN105017122A (en) * | 2015-07-08 | 2015-11-04 | 南京葆赫生物技术有限公司 | Anti-hypertension bioactive peptide, preparation method and application thereof |
-
2017
- 2017-07-26 CN CN201710619459.3A patent/CN107312064A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1623600A (en) * | 2003-12-04 | 2005-06-08 | 中国科学院大连化学物理研究所 | Inhibitor of angiotensin I transferase activity and its application |
| CN102399261A (en) * | 2010-09-07 | 2012-04-04 | 任发政 | Tripeptide with angiotensin converting enzyme C-terminal selective inhibition activity, application and composition thereof |
| CN102399262A (en) * | 2010-09-07 | 2012-04-04 | 任发政 | Tripeptides with angiotensin converting enzyme inhibition activity and their use and composition |
| CN104736552A (en) * | 2012-08-24 | 2015-06-24 | 庆熙大学校产学协力团 | Pharmaceutical composition comprising, as active ingredients, peptides which exhibit inhibitory activity against angiotensin-I converting enzyme for preventing or treating cardiovascular diseases |
| CN105001139A (en) * | 2015-07-08 | 2015-10-28 | 南京葆赫生物技术有限公司 | Antihypertensive active peptide, preparation method thereof and application thereof |
| CN105017122A (en) * | 2015-07-08 | 2015-11-04 | 南京葆赫生物技术有限公司 | Anti-hypertension bioactive peptide, preparation method and application thereof |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108358998A (en) * | 2018-04-25 | 2018-08-03 | 宁波大学 | A kind of siphon-worm peptide and its application in preparing gestation hypertension medicine |
| CN111848728A (en) * | 2019-04-30 | 2020-10-30 | 首都医科大学 | Preparation, activity and application of theanyl tetrahydroimidazopyridine-6-formyl-L-histidine |
| CN111848724A (en) * | 2019-04-30 | 2020-10-30 | 首都医科大学 | Preparation, activity and application of theanyl tetrahydroimidazopyridine-6-formyl acidic amino acid |
| CN111848724B (en) * | 2019-04-30 | 2022-04-22 | 首都医科大学 | Preparation, activity and application of theanyl tetrahydroimidazopyridine-6-formyl acidic amino acid |
| CN111848728B (en) * | 2019-04-30 | 2022-08-02 | 首都医科大学 | Preparation, activity and application of theanyl tetrahydroimidazopyridine-6-formyl-L-histidine |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103052717B (en) | Industrial production method for producing antihypertensive bioactive peptide | |
| EP3405477B1 (en) | Inhibitors of transglutaminases | |
| CN107312064A (en) | A kind of antihypertensive active peptide GABA The Pro and application and pharmaceutical composition | |
| CN103923177B (en) | A kind of inhibiting peptide of tonin of marine microalgae source | |
| CN104561207A (en) | Dual-enzyme hydrolysis preparation method of anti-tumor polypeptides of spirulina | |
| CN107337710A (en) | A kind of antihypertensive active peptide The The Pro and application and pharmaceutical composition | |
| CN105001139B (en) | A kind of antihypertensive active peptide, its preparation method and application | |
| CN105017122B (en) | A kind of antihypertensive active peptide, its preparation method and application | |
| CN107964034B (en) | The ultrasonic wave added simulation digestion method of casein active peptide and health food application | |
| CN108892710A (en) | Asparagus is depressured peptide extract and asparagus Antihypertensive Peptides and its application | |
| CN104805164A (en) | Preparation method of high protein oyster active peptides with low sensitization | |
| CN110669122B (en) | Preparation method of zein anti-inflammatory polypeptide | |
| CN107325153A (en) | A kind of antihypertensive active peptide Citn Hyp Pro and application and pharmaceutical composition | |
| CN107337712A (en) | A kind of antihypertensive active peptide Orn Hyp Pro and application and pharmaceutical composition | |
| CN107337711A (en) | A kind of antihypertensive active peptide Citn Pro Hyp and application and pharmaceutical composition | |
| CN102558298A (en) | Method for synthesizing tetrapeptide isomers by using solid phase peptide synthesis method and applications of tetrapeptide isomers | |
| CN104894198A (en) | Preparation method of hypoallergenic total-nutrient oyster active peptide | |
| CN106749524A (en) | A kind of anti-fat heptapeptide NPVWKRK | |
| Xia et al. | Screening of anti-liver fibrosis peptides from turtle shell protein using two-enzyme hydrolysis by molecular docking | |
| CN100352835C (en) | Corn albumen powder polypeptide, its separation method and uses | |
| CN113072621B (en) | Yak bone antihypertensive peptide and preparation method and application thereof | |
| CN111105845B (en) | Preparation of antihypertensive peptide based on protein folding fingerprint bar code design | |
| CN108484720A (en) | A kind of antihypertensive active peptide Orn-Pro-Hyp and application and pharmaceutical composition | |
| CN113912673A (en) | Low-bitter ACE inhibitory peptide derived from sesame, and preparation method and application thereof | |
| CN102787154A (en) | Preparation method of black-bone chicken oligopeptide and separation and identification method of active peptide fragment |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20171103 |
|
| RJ01 | Rejection of invention patent application after publication |