CN109180782A - A kind of biologically active polypeptide DDVTEVM and its preparation method and application - Google Patents
A kind of biologically active polypeptide DDVTEVM and its preparation method and application Download PDFInfo
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- CN109180782A CN109180782A CN201811036815.XA CN201811036815A CN109180782A CN 109180782 A CN109180782 A CN 109180782A CN 201811036815 A CN201811036815 A CN 201811036815A CN 109180782 A CN109180782 A CN 109180782A
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- ddvtevm
- biologically active
- active polypeptide
- polypeptide
- val
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- 230000035764 nutrition Effects 0.000 description 1
- 238000000399 optical microscopy Methods 0.000 description 1
- 230000004783 oxidative metabolism Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 238000005502 peroxidation Methods 0.000 description 1
- 108010064486 phenylalanyl-leucyl-valine Proteins 0.000 description 1
- 108010018625 phenylalanylarginine Proteins 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000009758 senescence Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 230000037380 skin damage Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
- 235000021247 β-casein Nutrition 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
- 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
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
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- 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
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
-
- 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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- Peptides Or Proteins (AREA)
Abstract
The present invention relates to albumen fields, and in particular to a kind of biologically active polypeptide DDVTEVM and its preparation method and application, its amino acid sequence of biologically active polypeptide DDVTEVM are Asp-Asp-Val-Thr-Glu-Val-Met.By antioxidation in vitro experiment, internal Antisenility Experiment, demonstrating polypeptide DDVTEVM has preferable antioxidation biology activity and activity of fighting against senium, on the one hand, biologically active polypeptide DDVTEVM of the invention has preferable antioxidant activity, can the intracorporal free radical of removing machine, improve the quality of life；On the other hand, it can be improved the vigor of internal anti-peroxidation enzyme system, enhance body and resist the function of external source sexual stimulus, to reduce organism aging process, aging and sick probability, there is anti-oxidation function, the food of anti-senescence function, health care product and drug to have a very important significance exploitation.
Description
Technical field
The present invention relates to albumen fields, more particularly, to a kind of biologically active polypeptide DDVTEVM and preparation method thereof and answer
With.
Background technique
During cow's milk is through lactobacillus-fermented, a part of protein in cow's milk is metabolized by lactic acid bacteria to be utilized, concurrently
A series of biochemical reactions have been given birth to, so that protein is become polypeptide or free amino acid, is digested or passes through
The absorption and transport of intestinal epithelial cell is directly entered the blood circulation of human body.There is also the eggs of itself some synthesis for lactic acid bacteria thallus
White matter polypeptide fragment is utilized for bacterial growth.In these polypeptides, some is referred to as " raw with special physiological function
Object active peptide ".
It is particularly important that safe biologically active peptide is found in natural food source.In recent years, it has been found that some foods
The polypeptides matter in object source has good bioactivity, such as corn small peptide, soybean peptide, cow's milk polypeptide.These polypeptides can
To be obtained by number of ways such as microbial fermentation, digestion enzymatic hydrolysis, and biologically active polypeptide is by 2~20 mostly
Amino acid residue composition, molecular weight are less than 6000Da, contain a certain amount of hydrophobic amino acid, aromatic amino acid.
Oxidation reaction and oxidative metabolism be all for food and human body it is vital, free radical and active oxygen cause
A series of oxidation reaction.When excessive free radical is formed, they can be more than protective enzyme such as superoxide dismutase, peroxide
Change the protective effect of hydrogen enzyme, is generated so as to cause a series of side effect such as lipid oxidation, Apoptosis.This kind of oxidations is anti-
It answers, not only influences the shelf-life of the food containing rouge, certain harm is also caused to the health of human body, such as rheumatic arthritis, sugar
Urinate disease, artery sclerosis etc..In addition, the generation of Collins et al. 2005 research discovery cancers also has with the oxidative damage of DNA
It closes.
Artificial synthesized antioxidants some in early days such as butylated hydroxy anisole (BHA), 2,6- di-t-butyl -4- methylbenzene
Phenol (BHT) is applied in food, as the antioxidant of lipid, but these artificial synthesized additives have for human body it is latent
Risk.In the research process of natural, from the anti-oxidation peptide of food proteins become popular research it
One.It is not only highly-safe, is easier to be absorbed and used than macro-nutrients such as protein, such as calcium, iron can be promoted micro-
The absorption of nutrient is measured, also there is preferable antioxidant activity, have a extensive future.
Aging is a natural phenomena, and process is often accompanied by the variation of antioxidant levels, organ-tissue, immune factor,
Complicated variation, such as the trend that proinflammatory cytokine IL-6, IL-4, TNF-α presentation increase, IL-6 occur for middle cell factor
It is all considered to play an important role in the generating process of geriatric disease with TNF-a.With science of heredity and molecular biology
Development, the research of biological decay mechanism achieve gratifying progress.Researcher pass through utilize some model organisms, as mouse,
The term single gene mutating experiment of drosophila and caenorhabditis elegan etc. finds that some genes can dramatically increase service life of these organisms and reach
As many as 6 times.
Anti-aging peptide in terms of physiological function there is amino acid cannot compare excellent as a kind of emerging antidotal agent
Gesture can generate promotion or inhibiting effect to the intracorporal enzyme of biology, improve absorption and benefit to minerals and other nutrients
With removing interior free yl enhances the resistance to oxidation of body itself, to delay senescence.Therefore, the nutrition and health care of biologically active peptide
Effect has become the emphasis of domestic and foreign scholars' subject study.Qiu Juan et al. warp experimental studies have found that, milk-derived bioactive micro peptide
Life span of drosophila melanogaster can effectively be extended, delay its aging, and also there is preferable antioxidation, thus it is speculated that may be wherein rich in coloured glaze
Base peptides.SOD vigor in serum, reduces its lipid in discovery bovine colostrum extract energy conspicuousness raising the elderly's body such as the brightness in week
Peroxide and enhancing body resistance to oxidation, have certain anti-senescence function.
Have much about the research of biologically active polypeptide at present, for example Chinese patent CN105254738A discloses one kind and comes
Derived from the milk-derived biologically active polypeptide DELQDKIH of beta-casein, Chinese patent CN105254739A discloses one kind and derives from
Milk-derived the biologically active polypeptide GTQYTD, Chinese patent CN105254740A of α s1- casein disclose a kind of from α s2-
The milk-derived biologically active polypeptide NQFYQKF of casein.
Summary of the invention
The purpose of the present invention is to provide a kind of biologically active polypeptide DDVTEVM and its preparation method and application.
The purpose of the present invention can be achieved through the following technical solutions:
First aspect present invention provides a kind of biologically active polypeptide DDVTEVM, amino acid sequence Asp-Asp-Val-
Thr-Glu-Val-Met, as shown in SEQ ID NO:1.
Preferably, the biologically active polypeptide derives from Lactobacillus helveticus mycoprotein.It is derive specifically from LBH_1154 |
m.1076 LBH_1154|g.1076 ORF LBH_1154|g.1076 LBH_1154|m.1076 type:5prime_
Partial len:554 (+) LBH_1154:1-1662 (+) albumen, and thus the 152nd~158, albumen amino acid it is residual
Base.LBH_1154|m.1076 LBH_1154|g.1076 ORF LBH_1154|g.1076 LBH_1154|m.1076 type:
5prime_partial len:554 (+) LBH_1154:1-1662 (+) protein amino acid sequence is as shown in SEQ ID NO:3.
LBH_1154|m.1076 LBH_1154|g.1076 ORF LBH_1154|g.1076 LBH_1154|m.1076
The amino acid sequence and corresponding core of type:5prime_partial len:554 (+) LBH_1154:1-1662 (+) albumen
Nucleotide sequence is existing technology, encodes the life of the nucleotide fragments energy encoding mature of this 152nd~158 amino acids residue of albumen
Object active peptides DDVTEVM.
Preferably, the biologically active polypeptide has anti-oxidation function and anti-senescence function.
Second aspect of the present invention provides the nucleotide fragments for encoding the biologically active polypeptide DDVTEVM, sequence
Are as follows: 5 '-tga tga tgt tac tga agt aat-3 ', as shown in SEQ ID NO:2.
Third aspect present invention provides the preparation method of the biologically active polypeptide DDVTEVM, can pass through gene work
The method of journey is artificial synthesized, can directly obtain from Lactobacillus helveticus thallus by the method that clasmatosis isolates and purifies, can be with
Directly prepared by chemical synthesis.
Fourth aspect present invention provides the food that the biologically active polypeptide DDVTEVM has anti-oxidation function in preparation
Application in product, health care product, drug or cosmetics.
Fifth aspect present invention provides the food that the biologically active polypeptide DDVTEVM has anti-senescence function in preparation
Application in product, health care product or drug.
Sixth aspect present invention provides the biologically active polypeptide DDVTEVM in preparation while having anti-oxidation function
With the application in the food, health care product or drug of anti-senescence function.
Specifically, biologically active polypeptide DDVTEVM of the invention, which can be used for preparing, reduces free radical to skin damage
Cosmetics, preparation have anti-oxidant and/or anti-aging drug；And due to biologically active polypeptide DDVTEVM of the invention
Product after being degraded by gastrointestinal tract still has bioactivity, therefore can be also used for preparing food such as Yoghourt, oxidation resistant
Health care product, and what is taken orally are used to prepare with anti-oxidant and/or anti-aging drug.
Seventh aspect present invention provides a kind of oxidation resistant product, including the biologically active polypeptide DDVTEVM or described
The derivative of biologically active polypeptide DDVTEVM；The oxidation resistant product includes antioxidant food, antioxidant health-care product, antioxygen
Chemical drug object or antioxidation cosmetic product；The derivative of the biologically active polypeptide DDVTEVM, refers in biologically active polypeptide
On the amino acid side groups of DDVTEVM, aminoterminal or c-terminus carry out hydroxylating, carboxylated, carbonylation, methylation, acetyl
The modification such as change, phosphorylation, esterification or glycosylation, obtained polypeptide derivative.
Eighth aspect present invention provides a kind of anti-aging product, including the biologically active polypeptide DDVTEVM or described
The derivative of biologically active polypeptide DDVTEVM；The anti-aging product includes antisenility cistanche food, antisenescence health product or anti-ageing
Old drug；The derivative of the biologically active polypeptide DDVTEVM, refers to the amino acid side chain in biologically active polypeptide DDVTEVM
On group, aminoterminal or c-terminus carry out hydroxylating, carboxylated, carbonylation, methylation, acetylation, phosphorylation, esterification or glycosyl
The modification such as change, obtained polypeptide derivative.
Ninth aspect present invention provides product that is a kind of while having anti-oxidation function and anti-senescence function, including institute
State the derivative of biologically active polypeptide DDVTEVM or the biologically active polypeptide DDVTEVM；With anti-oxidation function and anti-aging
The product of function includes food, health care product or drug；The derivative of the biologically active polypeptide DDVTEVM refers to living in biology
Property polypeptide DDVTEVM amino acid side groups on, aminoterminal or c-terminus carry out hydroxylating, carboxylated, carbonylation, methyl
The modification such as change, acetylation, phosphorylation, esterification or glycosylation, obtained polypeptide derivative.
Biologically active polypeptide DDVTEVM's of the present invention has the beneficial effect that biologically active polypeptide DDVTEVM of the invention has
Preferable antioxidant activity and activity of fighting against senium；On the one hand, biologically active polypeptide DDVTEVM of the invention has preferable antioxygen
Change activity, can the intracorporal free radical of removing machine, improve the quality of life；On the other hand, it can be improved internal antiperoxidase
The vigor of system, enhancing body resists the function of external source sexual stimulus, so that organism aging process, aging and sick probability are reduced, it is split
There is hair anti-oxidation function, the food of anti-senescence function, health care product and drug to have a very important significance.
Detailed description of the invention
Fig. 1: mass chromatography extracts figure (m/z=824.3479)；
Fig. 2: the second order ms figure for the segment that mass-to-charge ratio is 824.3479；
Fig. 3: polypeptide az, by crack conditions that mass-to-charge ratio is 824.3479；
Fig. 4: [DPPH] methanol standard curve；
Fig. 5: FeSO4Standard curve；
Fig. 6: each group experimental animal mouse spleen situation of change；
It (a) is low dosage stomach-filling group mouse spleen organization chart；It (b) is high dose stomach-filling group mouse spleen organization chart；
It (c) is naive mice spleen tissue；It (d) is animal model group mouse spleen organization chart；
Fig. 7: each group mice serum IL-6 variation table；
Fig. 8: each group mice serum TNF-α changes table.
Specific embodiment
Before further describing specific embodiments of the present invention, it should be appreciated that protection scope of the present invention is not limited to down
State specific specific embodiment；It is also understood that term used in the embodiment of the present invention is specific specific in order to describe
Embodiment, rather than limiting the scope of protection of the present invention.
When embodiment provides numberical range, it should be appreciated that except non-present invention is otherwise noted, two ends of each numberical range
Any one numerical value can be selected between point and two endpoints.Unless otherwise defined, the present invention used in all technologies and
Scientific term is identical as the normally understood meaning of those skilled in the art of the present technique.Except specific method, equipment used in embodiment,
Outside material, grasp and record of the invention according to those skilled in the art to the prior art can also be used and this
Any method, equipment and the material of the similar or equivalent prior art of method described in inventive embodiments, equipment, material come real
The existing present invention.
Unless otherwise stated, disclosed in this invention experimental method, detection method, preparation method be all made of this technology neck
Molecular biology, biochemistry, chromatin Structure and the analysis of domain routine, analytical chemistry, cell culture, recombinant DNA technology and
The routine techniques of related fields.These technologies have perfect explanation in the prior art, and for details, reference can be made to Sambrook etc.
MOLECULAR CLONING:A LABORATORY MANUAL, Second edition, Cold Spring Harbor
Laboratory Press, 1989and Third edition, 2001；Ausubel etc., CURRENT PROTOCOLS IN
MOLECULAR BIOLOGY, John Wiley&Sons, New York, 1987 and periodic updates；the
Series METHODS IN ENZYMOLOGY, Academic Press, San Diego；Wolffe, CHROMATIN
STRUCTURE AND FUNCTION, Third edition, Academic Press, San Diego, 1998；METHODS IN
ENZYMOLOGY, Vol.304, Chromatin (P.M.Wassarman and A.P.Wolffe, eds.), Academic
Press, San Diego, 1999；With METHODS IN MOLECULAR BIOLOGY, Vol.119, Chromatin
Protocols (P.B.Becker, ed.) Humana Press, Totowa, 1999 etc..
The present invention is described in detail with specific embodiment below in conjunction with the accompanying drawings.
1 active peptide DDVTEVM's of embodiment is artificial synthesized
One, the synthesis of biologically active peptide
1. RINK resin 3g (degree of substitution 0.3mmol/g) is weighed in the reactor of 150ml, with the methylene chloride of 50ml
(DCM) it impregnates.
After 2.2 hours, resin is washed with nitrogen-dimethylformamide (DMF) of 3 times of resin volumes, is then drained, so weight
It is four times multiple, it is stand-by after resin is drained.
3. a certain amount of 20% piperidines (piperidines/DMF=1:4, v:v) is added into reactor, it is placed on decolorization swinging table and shakes
20min is shaken, the Fmoc blocking group on resin is sloughed with this.It is washed four times after having taken off protection with the DMF of 3 times of resin volumes,
Then it drains.
4. taking the detection of a small amount of resin ninhydrin (nine well ninhydrins) method (each two drop of inspection A, inspection B, 100 DEG C of reactions
1min), resin has color, illustrates to be deprotected successfully.
5. it weighs amino acid Asp in right amount and 1- hydroxyl-benzene a pair of horses going side by side triazole (HOBT) is in right amount in the centrifuge tube of 50ml, addition
The DMF of 20ml is dissolved, and the N of 3ml is then added, N diisopropylcarbodiimide (DIC) oscillation shakes up 1min, clear to solution
It is added in reactor after clear, then reactor is placed in 30 DEG C of shaking table and is reacted.
After 6.2 hours, with a certain amount of acetic anhydride end socket (acetic anhydride: DIEA:DCM=1:1:2, v:v:v) half an hour, so
It is washed four times, is drained stand-by with the DMF of 3 times of resin volumes afterwards.
7. a certain amount of 20% piperidines (piperidines/DMF=1:4, v:v) is added into reactor, it is placed on decolorization swinging table and shakes
20min is shaken, the Fmoc blocking group on resin is sloughed with this.It is washed four times after having taken off protection with DMF, is then drained.
8. taking the detection of a small amount of resin ninhydrin (nine well ninhydrins) method (each two drop of inspection A, inspection B, 100 DEG C of reactions
1min), resin has color, illustrates to be deprotected successfully.
9. weighing second amino acid next in right amount and HOBT being in right amount in the centrifuge tube of 50ml, the DMF general of 25ml is added
It is dissolved, and the DIC oscillation that 2.5ml is then added shakes up 1min, is added in reactor after solution clarification, then by reactor
It is placed in 30 DEG C of shaking table and reacts.
After 10.1 hours, a small amount of resin is taken to detect, with ninhydrin method detection (each two drop of inspection A, inspection B, 100 DEG C of reactions
1min), if resin be it is colourless, illustrate fully reacting；If resin has color, illustrate condensation not exclusively, the reaction was continued.
11. after complete reaction, being washed resin four times with DMF, then drains, a certain amount of 20% is added into reactor
Piperidines (piperidines/DMF=1:4, v:v), be placed on decolorization swinging table and rock 20min, sloughs the Fmoc protecting group on resin with this
Group.It is washed four times after having taken off protection with DMF, then drains whether detection protection sloughs.
12. successively connecting amino acid Asp, Val, Thr, Glu, Val and Met according to step 9-11.
13. sloughing protection after connecting the last one amino acid, is washed four times with DMF, then taken out resin with methanol
It is dry.Then with 95 cutting liquids (trifluoroacetic acid: 1,2 dithioglycol: 3, isopropyl base silane: water=95:2:2:1, v:v:v) by polypeptide
It is cut down from resin (every gram of resin adds 10ml cutting liquid), and is centrifuged and is sunk with ice ether (cutting liquid: ether=1:9, v:v)
Drop four times.
So far, artificial synthesized biologically active peptide DDVTEVM.
Two, the confirmation of biologically active peptide
1) UPLC is analyzed
UPLC condition is as follows:
Instrument: Waters ACQUITY UPLC ultra high efficiency liquid phase-electron spray-level four bars-time of-flight mass spectrometer
Chromatographic column specification: BEH C18 chromatographic column
Flow velocity: 0.4mL/min
Temperature: 50 DEG C
Ultraviolet detection wavelength: 210nm
Sample volume: 2 μ L
Gradient condition: A liquid: contain the water of 0.1% formic acid (v/v), B liquid: containing the acetonitrile of 0.1% formic acid (v/v)
2) mass spectral analysis
Mass Spectrometry Conditions are as follows:
Ionic means: ES+
Mass range (m/z): 100-1000
Capillary voltage (Capillary) (kV): 3.0
Sampling spiroid (V): 35.0
Ion source temperature (DEG C): 115
It goes solvent temperature (DEG C): 350
It goes solvent stream (L/hr): 700.0
Collision energy (eV): 4.0
Sweep time (sec): 0.25
Interior sweep time (sec): 0.02
According to the above analysis method, using ultra high efficiency liquid phase-electron spray-level four bars-flight time mass spectrum, to bioactivity
Peptide D DVTEVM carries out chromatography and mass spectral analysis, and mass chromatography extraction figure is as shown in Figure 1, extract the second order ms at this peak
Figure and az, by crack conditions are as shown in Figures 2 and 3, and the polypeptide mass-to-charge ratio that can obtain this peak is 824.3479Da, and retention time is
52.5min。
3) result
From the figure 3, it may be seen that the case where being broken according to az, by, by Mascot software analytical calculation, obtains mass-to-charge ratio
The fragment sequence of 824.3479Da is Asp-Asp-Val-Thr-Glu-Val-Met (DDVTEVM), is denoted as SEQ ID NO:1.It should
Segment and LBH_1154 | m.1076 LBH_1154 | g.1076 ORF LBH_1154 | g.1076 LBH_1154 | m.1076
The residue sequence phase of type:5prime_partial len:554 (+) LBH_1154:1-1662 (+) the 152nd~158, albumen
It is corresponding, LBH_1154 | m.1076 LBH_1154 | g.1076 ORF LBH_1154 | g.1076 LBH_1154 | m.1076
Type:5prime_partial len:554 (+) LBH_1154:1-1662 (+) protein amino acid sequence is shown in SEQ ID NO:3.
The antioxidant activity of 2 biologically active peptide of embodiment is tested
One, the antioxidation activity in vitro of [DPPH] method measurement biologically active peptide DDVTEVM
1. experiment reagent and instrument:
Reagent: 1,1- diphenyl -2- trinitrophenyl-hydrazine (1,1-Diphenyl-2-picrylhydrazyl [DPPH]),
Japanese Wako company production；Methanol, Shanghai traditional Chinese medicines company provide；The biologically active polypeptide DDVTEVM that embodiment 1 obtains.
Key instrument: Sunrise microplate reader, Austrian Tecan Products；96 porocyte culture plates, the U.S.
The manufacture of Millipore company；Assay balance, Meitelei-tolido Products.
2. experimental method:
(1) 1mmol/L [DPPH] methanol solution
It weighs 0.349mg [DPPH] with assay balance to be dissolved in 1mL methanol solution, the 1mmol/L prepared
[DPPH] methanol solution, tinfoil are kept in dark place, i.e., with i.e. use.
(2) measurement of [DPPH] methanol standard curve
100 μ L [DPPH] methanol standard curve samples are separately added by table 1 in 96 orifice plates, are stored at room temperature 90min, are used
Microplate reader detects light absorption value at 517nm.
Table 1 [DPPH] methanol calibration curve solution is prepared
According to experimental result, using Excel matched curve and regression equation is calculated, as a result sees Fig. 4 (regression equation: y=-
0.192x+0.2271, R2=0.9991).The linear relationship of [DPPH] methanol standard curve is good, related coefficient 0.999,
Show that [DPPH] methanol standard curve preci-sion and accuracy meets testing requirements.In terms of result, absorbance value with
[DPPH] content is in inverse relation, and [DPPH] content is fewer, and light absorption value is higher, i.e., the ability that sample removes free radical is got over
By force.
(3) antioxidant activity of [DPPH] method measurement biologically active peptide DDVTEVM
1) sample sets: 80 μ L concentration are added in 96 orifice plates and add respectively for 1mmol/L [DPPH] methanol solution, by table 2
Enter sample to be tested (DDVTEVM), the positive control 1 (Trolox of 2.5mg/mL), positive control 2 of 20 μ L various concentrations
(Trolox of 0.025mg/mL) and negative control (phytic acid)；
2) blank group: being 1mmol/L [DPPH] methanol solution and 20 μ L so that 80 μ L concentration are added on same 96 orifice plate
The sample of deionized water does blank control.
After sample to be tested is loaded, it is stored at room temperature 90min, detects light absorption value at 517nm with microplate reader.Under
Formula calculates free radical scavenging activity, and experimental result is shown in Table 2.
Formula:
The antioxidant activity result of [DPPH] method of table 2 measurement biologically active polypeptide
From table 2 it can be seen that the Trolox of the 2.5mg/mL as positive control have under the same conditions it is strongest clear
Except the ability of free radical, free radical all in solution can be almost removed, is secondly Trolox, the phytic acid, work of 0.025mg/mL
Property polypeptide.It is 29.89% that polypeptide DDVTEVM, which removes [DPPH] free radical rate, and with the reduction of DDVTEVM concentration, clearly
Except free radical reduced capability.
2, FARP method measures biologically active peptide DDVTEVM antioxidant activity in vitro
1) experiment reagent and instrument
Total antioxidant capacity detection kit (Ferric Reducing Ability of Plasma FRAP method), is purchased from
Shanghai green skies biotechnology company；FeSO4Solution (10mmol/L), watermiscible vitamin E (Trolox solution) (10mmol/
L), the biologically active polypeptide DDVTEVM that embodiment 1 obtains.
Key instrument: Sunrise microplate reader, Austrian Tecan Products；96 porocyte culture plates, the U.S.
The manufacture of Millipore company；Assay balance, Meitelei-tolido Products；HWS26 type electric-heated thermostatic water bath, Shanghai
One permanent Science and Technology Ltd.'s manufacture.
2) experimental method
(1) preparation of FRAP working solution
According to total antioxidant capacity detection kit, TPTZ 7.5mL dilution, 750 μ L solution of TPTZ, detection are buffered
750 μ L of liquid is uniformly mixed, and is incubated in 37 DEG C of water-baths, is finished in 2 hours h.
(2)FeSO4The production of standard curve curve measures
180 μ LFRAP working solutions are first added in 96 orifice plates, 5 μ L FeSO are added by table 34Calibration curve solution is gently mixed
It is even, after 37 DEG C of incubation 3-5min, light absorption value is measured at 593nm with microplate reader.
3 FeSO of table4The solution of standard curve determination is prepared
FeSO4Concentration and light absorption value are in good proportional relation, FeSO4Concentration is higher, and light absorption value is higher.FeSO of the present invention4
Standard curve result is shown in Fig. 5, and the linear relationship of standard curve is good, related coefficient 0.998, FeSO4The precision of standard curve
Degree and accuracy meet testing requirements, can be used for subsequent calculating.
(3) oxidation resistance of FRAP method measurement biologically active polypeptide DDVTEVM
180 μ L FRAP working solutions are first added in 96 orifice plates, 5 μ L ddH are added in blank control wells2O, sample detection hole
5 μ L phytic acid are added in 5 μ L samples to be tested of interior addition, positive control, mixes gently, after 37 DEG C of incubation 3-5min, is existed with microplate reader
Light absorption value is measured at 593nm.Total antioxidant capacity representation is with FeSO4The concentration of standard solution indicates.It counts according to the following formula
Free radical scavenging activity is calculated, experimental result is shown in Table 4.
The total antioxidant capacity result of 4 FARP method of table measurement biologically active polypeptide DDVTEVM
By total antioxidant capacity method (Ferric Reducing Ability Power FRAP method) to polypeptide DDVTEVM
External total antioxidant activity be determined, discovery biologically active polypeptide DDVTEVM has preferable reduction-oxidation substance
Ability；When concentration is 4mg/mL, the total antioxidation level of polypeptide DDVTEVM reaches 0.0233mmol/g；Illustrate biology
The total antioxidant capacity of active peptides DDVTEVM has significant higher than the phytic acid with weak antioxidant activity under comparable sodium
Property (p > 0.05) difference.Therefore, it can assert that the biologically active polypeptide DDVTEVM of invention has significant oxidation resistance.
The activity of fighting against senium of 3 biologically active peptide of embodiment is tested
One, experiment of the biologically active polypeptide DDVTEVM to internal spleen tissue structure function
1. experiment reagent and instrument:
Reagent: experimental animal ICR mouse (male 5 week old), Shanghai City Experimental Animal Center；D-gal, Chinese medicines group chemistry
Reagent Co., Ltd；Paraformaldehyde, Sinopharm Chemical Reagent Co., Ltd.；Sodium chloride, the limited public affairs of Chinese medicines group chemical reagent
Department；The biologically active polypeptide DDVTEVM that embodiment 1 obtains.
Instrument and equipment: the ultra-clean water of CM-230 type mole, Shanghai Moller scientific instrument Co., Ltd；Mi Libo Millipore
MILLEX GP0.22 μm filter membrane, Millipore Corp. of the U.S.；GL-22M high speed freezing centrifuge, Shanghai Lu Xiang instrument centrifuge instrument
Co., Ltd.
2. experimental method:
(1) Animal Aging model modeling
After a week by ICR mouse adaptive feeding, it is divided into 4 groups, every group 6.Group 1 is low dosage stomach-filling group, and mouse is daily
D-gal is subcutaneously injected with the dosage the nape of the neck of 500mg/kg, and with the dosage stomach-filling biologically active polypeptide in 1mg/ day
DDVTEVM；Group 2 is high dose stomach-filling group, and D-gal is subcutaneously injected daily with the dosage the nape of the neck of 500mg/kg in mouse, and
The day dosage stomach-filling biologically active polypeptide DDVTEVM of 3mg/ only；Group 3 is blank group, mouse normal growth；Group 4 is animal mould
D-gal, and the physiology salt that stomach-filling concentration is 0.9% is subcutaneously injected daily with the dosage the nape of the neck of 500mg/kg in type group, mouse
Water；The injection cycle of D-gal and the stomach-filling period of polypeptide are 42 days.Every 3 days replacement paddings, and guarantee feed and distilled water
Supply.The weight for weighing a mouse for every five days prepares D-gal injection according to the weight of mouse, and D-gal injection passes through
0.22 μm of needle cylinder type filter membrane filtering, it is sterile to guarantee.
(2) animal viscera is obtained
After the completion of experimental period, to pluck the blood that eyeball blood taking method obtains mouse, disconnected neck puts to death mouse after obtaining blood, and
The body of mouse is placed on low temperature ice box afterwards, and wins brain, spleen, liver and the kidney of mouse rapidly, it is obtained dirty
Device is placed in the 1.5mL centrifuge tube to sterilize in advance, and all organ samples are maintained in -80 DEG C of refrigerators standby inspection.Disposition is real
All operations tested during animal follow " the directiveness meaning about kind treatment experimental animal of Ministry of Science and Technology's publication in 2006
See ".The mouse spleen won directly is soaked in preparatory prepared 4% paraformaldehyde solution, to fix in the form of it.Poly
Formaldehyde powder more indissoluble can be added micro sodium bicarbonate and pH value is adjusted to alkalinity, with hydrotropy.Paraformaldehyde solution
It prepares and needs to complete in draught cupboard.
(3) sample detection
The production of histotomy: mouse spleen sample need at least fix 24 hours in 4% paraformaldehyde solution.Spleen group
Wax stone production, slice and HE the dyeing commission Shanghai Wei Ao Biotechnology Co., Ltd knitted complete.
3. experimental result and analysis:
In this experiment, 4 groups of mouse are shared, wherein the mouse normal growth of blank group is not affected by any environmental stimuli,
3 groups of mouse of remaininging receive the long term injections of D-gal.Using optical microscopy, the spleen section of separate groups of mice is seen
It examines, can be found from Fig. 6, compare the spleen section of each group mouse, for naive mice, the spleen of animal model mouse
Dirty red pulp and white pulp boundary are fuzzy, and atrophy occurs in white pulp, show that the glycometabolism approach of mouse occurs for long-term D-gal injection
Disorder causes anti-oxidant enzyme activity to reduce, peroxide accumulation, and then may cause the aging and atrophy of spleen.And stomach-filling is more
Then white pulp atrophy degree is lighter relative to animal model group mouse for the spleen tissue of the mouse of peptide group, and the boundary of red pulp and white pulp
It is more clearly demarcated.This result explanation, in the injection cycle of entire D-gal, experiment animal sustained is constantly by cause senescence-factor
Stimulation, lead to the aging and atrophy of spleen.Therefore from the changes in microstructure the case where from the point of view of, the biology invented in this experiment
Active peptides DDVTEVM is to animal because the spleen aging caused by the stimulation by the bad factor has certain protection with atrophy
Effect.
Two, the experiment that biologically active polypeptide DDVTEVM acts on intracorporeal organ antioxidant levels
1. experiment reagent and instrument:
Reagent: experimental animal ICR mouse (male 5 week old), Shanghai City Experimental Animal Center；D-gal, Chinese medicines group chemistry
Reagent Co., Ltd；Paraformaldehyde, Sinopharm Chemical Reagent Co., Ltd.；Sodium chloride, the limited public affairs of Chinese medicines group chemical reagent
Department；The biologically active polypeptide DDVTEVM that embodiment 1 obtains；BCA protein reagent box, Science and Technology Ltd. of Nanjing Keygen Biotech；
MDA lipid peroxide kit, Science and Technology Ltd. of Nanjing Keygen Biotech；SOD superoxide dismutase kit, Nanjing is built
At Biotechnology Co., Ltd.
Instrument and equipment: the ultra-clean water of CM-230 type mole, Shanghai Moller scientific instrument Co., Ltd；Mi Libo Millipore
MILLEX GP0.22 μm filter membrane, Millipore Corp. of the U.S.；GL-22M high speed freezing centrifuge, Shanghai Lu Xiang instrument centrifuge instrument
Co., Ltd.
2. experimental method:
(1) Animal Aging model modeling
After a week by ICR mouse adaptive feeding, it is divided into 4 groups, every group 6.Group 1 is low dosage stomach-filling group, and mouse is daily
D-gal is subcutaneously injected with the dosage the nape of the neck of 500mg/kg, and with the dosage stomach-filling biologically active polypeptide in 1mg/ day
DDVTEVM；Group 2 is high dose stomach-filling group, and D-gal is subcutaneously injected daily with the dosage the nape of the neck of 500mg/kg in mouse, and
The day dosage stomach-filling biologically active polypeptide DDVTEVM of 3mg/ only；Group 3 is blank group, mouse normal growth；Group 4 is animal mould
D-gal, and the physiology salt that stomach-filling concentration is 0.9% is subcutaneously injected daily with the dosage the nape of the neck of 500mg/kg in type group, mouse
Water；The injection cycle of D-gal and the stomach-filling period of polypeptide are 42 days.Every 3 days replacement paddings, and guarantee feed and distilled water
Supply.The weight for weighing a mouse for every five days prepares D-gal injection according to the weight of mouse, and D-gal injection passes through
0.22 μm of needle cylinder type filter membrane filtering, it is sterile to guarantee.
(2) animal viscera is obtained
After the completion of experimental period, to pluck the blood that eyeball blood taking method obtains mouse, disconnected neck puts to death mouse after obtaining blood, and
The body of mouse is placed on low temperature ice box afterwards, and wins brain, spleen, liver and the kidney of mouse rapidly, it is obtained dirty
Device is placed in the 1.5mL centrifuge tube to sterilize in advance, and all organ samples are maintained in -80 DEG C of refrigerators standby inspection.Disposition is real
All operations tested during animal follow " the directiveness meaning about kind treatment experimental animal of Ministry of Science and Technology's publication in 2006
See ".The mouse spleen won directly is soaked in preparatory prepared 4% paraformaldehyde solution, to fix in the form of it.Poly
Formaldehyde powder more indissoluble can be added micro sodium bicarbonate and pH value is adjusted to alkalinity, with hydrotropy.Paraformaldehyde solution
It prepares and needs to complete in draught cupboard.
(3) sample detection
All internal organs that need to be detected, grind at low ambient temperatures, and 10% group is diluted to 4 DEG C of sterile PBS solutions
Homogenate is knitted, under the conditions of 4 DEG C after 4000g centrifugation, supernatant is taken, discards precipitating, operated according to kit specification, or set
It is to be measured in -80 DEG C of refrigerators.
3. experimental result and analysis:
The variation of SOD content in 5 each group experimental animal mouse Different Organs of table
Note: * mark is compared with model group, there is significant difference (P < 0.05)；* mark is compared with model group,
There is significant difference (P < 0.01), similarly hereinafter.
As can be known from Table 5, relative to animal model group mouse, the SOD in the liver and kidney of polypeptide stomach-filling group mouse contains
The increase (P < 0.01) of conspicuousness is presented in amount.Although meaning D-gal of the mouse of polypeptide stomach-filling group by long-term, high-dose
Stimulation, the excess injection of D-gal without completely destroy Mice Body in SOD enzyme system, illustrate in injection cycle, experiment
Animal will lead to the reduction of SOD content in Different Organs, but same continuously by the stimulation for causing senescence-factor
When take in a certain amount of polypeptide DDVTEVM to the intracorporal oxidative damage of mouse have certain protective role.
The situation of change of MDA content in 6 each group experimental animal mouse Different Organs of table
As can be known from Table 6, the liver MDA content of animal model group mouse is 26.92 ± 4.09nmol/L, with animal model
Group compares, and significant difference (P < 0.01) is presented in the MDA content in two groups of mouse livers of polypeptide stomach-filling.Since MDA can be used for
Estimate the accumulation situation of animal body lipid peroxide, therefore it follows that animal model group mouse is causing aging model to be formed
In the process, due to the long term injections of excessive D-gal, the glycometabolism approach of mouse is made to get muddled, generate a large amount of free radicals from
And oxidative damage is caused, occur a large amount of lipid peroxide in liver organization, MDA is as lipid peroxide, in animal
The raising of in-vivo content can reflect the reduction of Antioxidant Enzymes vigor in Mice Body from side.And polypeptide stomach-filling group Mouse Liver
The significant decrease of dirty MDA content illustrates that the intake of polypeptide DDVTEVM can be effectively protected vital tissue organ from the bad factor
Stimulation generates a large amount of lipid peroxide.
Three, the experiment that immune cell factor in serum is acted on of biologically active polypeptide DDVTEVM
1. experiment reagent and instrument:
Reagent: experimental animal ICR mouse (male 5 week old), Shanghai City Experimental Animal Center；D-gal, Chinese medicines group chemistry
Reagent Co., Ltd；Paraformaldehyde, Sinopharm Chemical Reagent Co., Ltd.；Sodium chloride, the limited public affairs of Chinese medicines group chemical reagent
Department；The biologically active polypeptide DDVTEVM that embodiment 1 obtains；BCA protein reagent box, Science and Technology Ltd. of Nanjing Keygen Biotech；
ELISA cell factor Quick kit (TNF-α and IL-6), Wuhan Boster Biological Technology Co., Ltd..
Instrument and equipment: the ultra-clean water of CM-230 type mole, Shanghai Moller scientific instrument Co., Ltd；Mi Libo Millipore
MILLEX GP0.22 μm filter membrane, Millipore Corp. of the U.S.；GL-22M high speed freezing centrifuge, Shanghai Lu Xiang instrument centrifuge instrument
Co., Ltd.
2. experimental method:
(1) Animal Aging model modeling
After a week by ICR mouse adaptive feeding, it is divided into 4 groups, every group 6.Group 1 is low dosage stomach-filling group, and mouse is daily
D-gal is subcutaneously injected with the dosage the nape of the neck of 500mg/kg, and with the dosage stomach-filling biologically active polypeptide in 1mg/ day
DDVTEVM；Group 2 is high dose stomach-filling group, and D-gal is subcutaneously injected daily with the dosage the nape of the neck of 500mg/kg in mouse, and
The day dosage stomach-filling biologically active polypeptide DDVTEVM of 3mg/ only；Group 3 is blank group, mouse normal growth；Group 4 is animal mould
D-gal, and the physiology salt that stomach-filling concentration is 0.9% is subcutaneously injected daily with the dosage the nape of the neck of 500mg/kg in type group, mouse
Water；The injection cycle of D-gal and the stomach-filling period of polypeptide are 42 days.Every 3 days replacement paddings, and guarantee feed and distilled water
Supply.The weight for weighing a mouse for every five days prepares D-gal injection according to the weight of mouse, and D-gal injection passes through
0.22 μm of needle cylinder type filter membrane filtering, it is sterile to guarantee.
(2) animal viscera and serum are obtained
After the completion of experimental period, to pluck the blood that eyeball blood taking method obtains mouse, disconnected neck puts to death mouse after obtaining blood, and
The body of mouse is placed on low temperature ice box afterwards, after mouse blood is stored at room temperature 1 hour, 15min is centrifuged with 3000g, separates blood
Clearly.Serum keeping is to be checked in -80 DEG C of refrigerators.All operations during disposition experimental animal follow the Ministry of Science and Technology in 2006
" the guiding opinion about kind treatment experimental animal " of publication.The mouse spleen won directly is soaked in prepared in advance
In 4% paraformaldehyde solution, to fix in the form of it.Paraformaldehyde powder more indissoluble, micro sodium bicarbonate can be added will
PH value is adjusted to alkalinity, with hydrotropy.The preparation needs of paraformaldehyde solution are completed in draught cupboard.
(3) sample detection
It is indicated according to kit specification, first drafting standard curve, standard items powder is prepared with standard dilutions
At the solution of 1000pg/mL, then serial dilution is 500pg/mL, 250pg/mL, 125pg/mL, 62.5pg/mL, 31.3pg/mL,
15.6pg/mL waiting various concentrations.Each concentration gradient solution pipettes 100 μ L in the ELISA Plate of coated antibody.Draw mouse
100 μ L of blood serum sample, be added in same ELISA Plate (need to press when detecting calculating again if blood serum sample is inadequate, after can suitably diluting
Ratio conversion).ELISA Plate is covered, places it under 37 DEG C of environment and is incubated for 90min.After completion of the reaction, it carefully gets rid of in ELISA Plate
Liquid, and ELISA Plate is placed on blotting paper, it is careful to pat, remove surplus liquid.By preheated biotin antiantibody work
Make liquid to sequentially add in each hole of ELISA Plate by every 100 μ L of hole, at 37 DEG C, reacts 60min.After completion of the reaction, utilize 0.01M's
PBS solution is washed 3 times, and the PBS of 100 μ L is added in each every hole, is impregnated 1min hypsokinesis and is removed solution, and 3 times repeatedly.It will be preheated
ABC working solution is sequentially added by every hole 0.1ml, 37 DEG C of reaction 30min.After completion of the reaction, 5 times are washed with 0.01M PBS, every time
Impregnate 1min or so.The TMB developing solution for balancing 30min at 37 DEG C is sequentially added by every 90 μ L of hole, 37 DEG C are protected from light 8-
12min.TMB terminate liquid is sequentially added by every hole 0.1ml, blue is vertical at this time turns yellow, measures OD value in 450nm with microplate reader.
Known concentration is done by the standard protein of cell factor to be serially diluted, draws out standard curve after measuring OD value, according to standard song
Line can extrapolate the content of cell factor in sample.
3. experimental result and analysis:
The situation of change of cell factor in 7 each group mice serum of table
IL-6 and TNF-α content are respectively out of model group Mice Body that can be found that in this experiment in table 7, Fig. 7, Fig. 8
167.34 ± 24.28pg/mL, 4.31 ± 0.69pg/mL, compared to the increase (P < 0.01) that conspicuousness is presented in normal group, therefore
It is considered that causing animal model group mouse aging occur in cell factor level due to continuously injecting cause senescence-factor
The symptom of property inflammation, and the IL-6 of the mice serum of polypeptide stomach-filling group is effectively controlled with TNF-α content.According to cell because
The experimental result of son, the serum levels of inflammatory cytokines IL-6 of polypeptide stomach-filling group mouse, the secretion level of TNF-α are below animal mould
Type group, from the point of view of oxidative damage angle, mouse because free radical attack, Peroxidation Product accumulation due to caused by oxidative damage may obtain
Inhibition to a certain extent；From the perspective of inflammation, mouse inflammation because of caused by oxidation has obtained effective inhibition；From declining
From the point of view of old angle, a series of geriatric diseases caused by mouse aging by caused by long term injections D-gal are possible to obtain
Control.
The above description of the embodiments is intended to facilitate ordinary skill in the art to understand and use the invention.
Person skilled in the art obviously easily can make various modifications to these embodiments, and described herein general
Principle is applied in other embodiments without having to go through creative labor.Therefore, the present invention is not limited to the above embodiments, ability
Field technique personnel announcement according to the present invention, improvement and modification made without departing from the scope of the present invention all should be of the invention
Within protection scope.
Sequence table
<110>Shanghai Communications University；Zhejiang Hui Tai life and health Science and Technology Ltd.
<120>a kind of biologically active polypeptide DDVTEVM and its preparation method and application
<160> 3
<170> SIPOSequenceListing 1.0
<210> 1
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<212> PRT
<213>artificial sequence (Artificial Sequence)
<400> 1
Asp Asp Val Thr Glu Val Met
1 5
<210> 2
<211> 21
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 2
tgatgatgtt actgaagtaa t 21
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<211> 553
<212> PRT
<213>artificial sequence (Artificial Sequence)
<400> 3
Val Val Leu Asn Glu Ile Gly Ser Lys Gln Phe Arg Asp Met Val Arg
1 5 10 15
Val Ala Thr His Arg Ile Gly Lys Asn Ala Glu Phe Val Asn Ser Leu
20 25 30
Asn Val Phe Pro Val Pro Asp Gly Asp Thr Gly Thr Asn Met Asn Leu
35 40 45
Thr Ile Glu Ser Gly Ala Lys Ala Val Ser Glu Asn Pro Ser Thr Ser
50 55 60
Val Gly Asp Leu Thr Glu Ser Leu Ala Lys Gly Met Leu Met Gly Ala
65 70 75 80
Arg Gly Asn Ser Gly Val Ile Thr Ser Gln Leu Phe Arg Gly Phe Tyr
85 90 95
Lys Ala Thr Gln Gly Met Lys Thr Leu Thr Ala Gln Glu Leu Ala Asn
100 105 110
Ala Phe Ser Asn Gly Val Ala Thr Ala Tyr Lys Ala Val Met Lys Pro
115 120 125
Val Glu Gly Thr Ile Leu Thr Val Ala Arg Val Ala Ala Gln Glu Gly
130 135 140
Ala Asn Lys Ala Asn Asp Thr Asp Asp Val Thr Glu Val Met Gln Ala
145 150 155 160
Val Val Glu Gly Ala Lys Lys Ala Leu Lys Ser Thr Pro Asp Leu Leu
165 170 175
Pro Val Leu Lys Gln Val Gly Val Val Asp Ser Gly Gly Gln Gly Leu
180 185 190
Leu Phe Ile Tyr Glu Gly Phe Leu Glu Gly Ile Leu Gly Glu Asn Phe
195 200 205
Ala Asp Gln Tyr Gln Pro Asp Glu Asn Glu Met Asp Glu Met Ile Asn
210 215 220
Ala Met His His Gln Ser Ser Val Gln Ser Gln Leu Ala Thr Gln Asp
225 230 235 240
Ile Lys Asn Gly Tyr Cys Thr Glu Ile Met Val Asp Leu Asn Ala Asp
245 250 255
Val Pro Asn Lys Lys Lys Phe Asp Leu Glu Glu Phe Arg Lys His Leu
260 265 270
Ser Gly Leu Gly Asp Ser Leu Leu Ala Val Ser Asp Gly Glu Ile Ala
275 280 285
Lys Val His Val His Thr Glu His Pro Gly Asp Val Phe Gln Tyr Gly
290 295 300
Ser Gln Phe Gly Gln Leu Gly Lys Ile Lys Ile Asp Asn Met Arg Ile
305 310 315 320
Gln His Glu Ser Ile Val Asp Gln Asp Lys Glu Gln Gln Glu Ala Val
325 330 335
Asp Phe Ala Val Ile Ala Val Ala Ser Gly Asn Gly Ile Arg Lys Leu
340 345 350
Phe Glu Ser Glu Gly Val Asn Arg Ile Ile Ser Gly Gly Gln Thr Met
355 360 365
Asn Pro Ser Thr Gln Asp Phe Ile Asp Ala Ile Lys Lys Ser Gly Ala
370 375 380
Lys Lys Ala Leu Leu Leu Pro Asn Asn Gly Asn Ile Ile Met Ala Ala
385 390 395 400
Lys Gln Ala Ala Glu Val Ser Asp Ile Pro Val Gly Val Val Pro Thr
405 410 415
Lys Thr Ile Ser Gln Gly Leu Thr Ala Met Leu Ser Phe Asp Pro Val
420 425 430
Ala Ser Val Asp Glu Asn Val Glu Ala Met Ser Asp Glu Leu Asp Thr
435 440 445
Val Val Ser Gly Glu Val Thr Gln Ala Thr Arg Asp Thr Glu Ile Asp
450 455 460
Asn Val Glu Ile His Lys Asp Asp Tyr Leu Gly Ile Val Asp Gly Ser
465 470 475 480
Ile Lys Val Asp Asn Ala Asp Leu Ile Lys Thr Thr Thr Glu Met Ile
485 490 495
Glu Lys Met Leu Asp Asp Asp Ser Glu Ile Ile Thr Ile Met Tyr Gly
500 505 510
Arg Asp Ala Ser Glu Asp Glu Ala Gln Gln Val Val Glu Ala Leu Glu
515 520 525
Ala Asn His Asp Asp Leu Glu Phe Glu Ile His Asp Gly Gly Gln Pro
530 535 540
Val Tyr Tyr Phe Leu Val Ser Val Glu
545 550
Claims (10)
1. a kind of biologically active polypeptide DDVTEVM, which is characterized in that its amino acid sequence is Asp-Asp-Val-Thr-Glu-
Val-Met。
2. a kind of biologically active polypeptide DDVTEVM according to claim 1, which is characterized in that the biologically active polypeptide
From Lactobacillus helveticus mycoprotein.
3. encoding the nucleotide fragments of biologically active polypeptide DDVTEVM described in claim 1, which is characterized in that the nucleotide
The sequence of segment is as shown in SEQ ID NO:2.
4. the preparation method of biologically active polypeptide DDVTEVM as described in claim 1, which is characterized in that pass through genetic engineering
Method is artificial synthesized or Lactobacillus helveticus thallus is directly obtained by the method that clasmatosis isolates and purifies, or directly passing through
Be synthetically prepared.
5. the application of biologically active polypeptide DDVTEVM as described in claim 1, which is characterized in that the biologically active polypeptide
Application of the DDVTEVM in food, health care product, drug or the cosmetics that preparation has anti-oxidation function.
6. the application of biologically active polypeptide DDVTEVM as described in claim 1, which is characterized in that the biologically active polypeptide
Application of the DDVTEVM in the food, health care product or drug that preparation has anti-senescence function.
7. the application of biologically active polypeptide DDVTEVM as described in claim 1, which is characterized in that the biologically active polypeptide
Application of the DDVTEVM in the food, health care product or drug that preparation has anti-oxidation function and anti-senescence function.
8. a kind of oxidation resistant product, which is characterized in that including biologically active polypeptide DDVTEVM or described as described in claim 1
The derivative of biologically active polypeptide DDVTEVM；The oxidation resistant product includes antioxidant food, antioxidant health-care product, antioxygen
Chemical drug object or antioxidation cosmetic product；The derivative of the biologically active polypeptide DDVTEVM, refers in biologically active polypeptide
On the amino acid side groups of DDVTEVM, aminoterminal or c-terminus carry out hydroxylating, carboxylated, carbonylation, methylation, acetyl
Change, phosphorylation, esterification or glycosylation modified, obtained polypeptide derivative.
9. a kind of anti-aging product, which is characterized in that including biologically active polypeptide DDVTEVM or described as described in claim 1
The derivative of biologically active polypeptide DDVTEVM；The anti-aging product includes antisenility cistanche food, antisenescence health product or anti-ageing
Old drug；The derivative of the biologically active polypeptide DDVTEVM, refers to the amino acid side chain in biologically active polypeptide DDVTEVM
On group, aminoterminal or c-terminus carry out hydroxylating, carboxylated, carbonylation, methylation, acetylation, phosphorylation, esterification or glycosyl
Change modification, obtained polypeptide derivative.
10. a kind of product with anti-oxidation function and anti-senescence function, which is characterized in that including giving birth to as described in claim 1
The derivative of object active peptides DDVTEVM or the biologically active polypeptide DDVTEVM；With anti-oxidation function and anti-senescence function
Product include food, health care product or drug；The derivative of the biologically active polypeptide DDVTEVM refers to more in bioactivity
On the amino acid side groups of Peptide D DVTEVM, aminoterminal or c-terminus carry out hydroxylating, carboxylated, carbonylation, methylation, second
Acylation, phosphorylation, esterification or glycosylation modified, obtained polypeptide derivative.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009121176A1 (en) * | 2008-03-31 | 2009-10-08 | The University Of British Columbia | Insulin-induced gene (insig) peptide compositions and methods for cytoprotection |
| CN105254750A (en) * | 2015-10-16 | 2016-01-20 | 上海交通大学 | Bioactive polypeptide FGYSGAFKCL as well as preparation and application thereof |
-
2018
- 2018-09-06 CN CN201811036815.XA patent/CN109180782B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009121176A1 (en) * | 2008-03-31 | 2009-10-08 | The University Of British Columbia | Insulin-induced gene (insig) peptide compositions and methods for cytoprotection |
| CN105254750A (en) * | 2015-10-16 | 2016-01-20 | 上海交通大学 | Bioactive polypeptide FGYSGAFKCL as well as preparation and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| JIEHUI,ZHOU 等: "Immunomodulating effects of casein-derived peptides QEPVL and QEPV on lymphocytes in vitro and in vivo", 《FOOD & FUNCTION》 * |
| 钱蕙佶等: "瑞士乳杆菌胞内生物活性肽的分离鉴定", 《中国乳品工业》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111100196A (en) * | 2019-11-08 | 2020-05-05 | 上海交通大学 | Bioactive polypeptide QILSVPGWTYSR, and preparation method and application thereof |
| CN111100196B (en) * | 2019-11-08 | 2021-07-13 | 上海交通大学 | Bioactive polypeptide QILSVPGWTYSR, and preparation method and application thereof |
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| Publication number | Publication date |
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| CN109180782B (en) | 2021-03-23 |
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Address after: 200030 Dongchuan Road, Minhang District, Minhang District, Shanghai Applicant after: Shanghai Jiaotong University Applicant after: Zhejiang peptide life health science and Technology Co Ltd Address before: 200030 Huashan Road, Shanghai, No. 1954, No. Applicant before: Shanghai Jiaotong University Applicant before: Zhejiang peptide life health science and Technology Co Ltd |
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