CN107880105A - A kind of biologically active polypeptide VPITPTLNR and its preparation method and application - Google Patents
A kind of biologically active polypeptide VPITPTLNR and its preparation method and application Download PDFInfo
- Publication number
- CN107880105A CN107880105A CN201711310260.9A CN201711310260A CN107880105A CN 107880105 A CN107880105 A CN 107880105A CN 201711310260 A CN201711310260 A CN 201711310260A CN 107880105 A CN107880105 A CN 107880105A
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- China
- Prior art keywords
- vpitptlnr
- biologically active
- active polypeptide
- polypeptide
- derivative
- Prior art date
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4732—Casein
-
- 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
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Birds (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Dermatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
The present invention relates to albumen field, and in particular to its amino acid sequence of a kind of biologically active polypeptide VPITPTLNR and its preparation method and application, biologically active polypeptide VPITPTLNR is Val Pro Ile Thr Pro Thr Leu Asn Arg.Tested by antioxidation in vitro, internal Antisenility Experiment, demonstrating polypeptide VPITPTLNR has preferable antioxidation biology activity and activity of fighting against senium, on the one hand, the biologically active polypeptide VPITPTLNR of the present invention has preferable antioxidation activity, free radical that can be in removing machine body, improve the quality of life；On the other hand, the vigor of internal anti-peroxidation enzyme system can be improved, strengthen the function of body resistance external source sexual stimulus, so as to reduce organism aging process, aging and sick probability, exploitation is of great significance with anti-oxidation function, the food of anti-senescence function, health products and medicine tool.
Description
Technical field
The present invention relates to albumen field, more particularly, to a kind of biologically active polypeptide VPITPTLNR and preparation method thereof and
Using.
Background technology
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, protein is changed into 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.In these polypeptides, some has special
Physiological function, it is referred to as " biologically active peptide ".
It is particularly important that safe biologically active peptide is found in natural food source.In the last few years, it has been found that some foods
The polypeptides matter in thing 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 enzymolysis, and the polypeptide with bioactivity is by 2~20 mostly
Amino acid residue forms, and molecular weight is less than 6000Da, contains a certain amount of hydrophobic amino acid, aromatic amino acid.
Oxidation reaction and oxidative metabolism are all vital for food and human body, and free radical and active oxygen cause
A series of oxidation reaction.When the free radical of excess is formed, they can exceed protective enzyme such as superoxide dismutase, peroxide
Change the protective effect of hydrogen enzyme, so as to cause a series of side effect such as lipid oxidation, Apoptosis to produce.This kind of oxidation is anti-
Should, the shelf-life of the food containing fat is not only influenceed, certain harm also is caused to the health of human body, such as rheumatic arthritis, sugar
Urinate disease, artery sclerosis etc..In addition, Collins et al. researchs in 2005 find that oxidative damage of the generation of cancer also with DNA has
Close.
Some artificial synthesized antioxidant such as butylated hydroxy anisoles (BHA), 2,6- di-t-butyl -4- methylbenzenes in early days
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 safe, is easier to be absorbed and used than macro-nutrients such as protein, and such as calcium, iron can be promoted micro-
The absorption of nutrient is measured, also with preferable antioxidation activity, is had a extensive future.
Aging is a natural phenomena, and process is often accompanied by the change of antioxidant levels, organ-tissue, immune factor, its
The change of complexity, the trend that such as 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 by using some model organisms, as mouse,
The term single gene mutating experiment of drosophila and C. Elegans Automatic Screening etc., it is found that some genes can dramatically increase life-spans of these organisms and reach
As many as 6 times.
Anti-aging peptide in terms of physiological function there is amino acid can not compare excellent as a kind of emerging antidotal agent
Gesture, it can produce promotion or inhibitory action to the enzyme in organism, improve absorption and the profit to mineral matter and other nutrients
With, removing interior free yl, the resistance to oxidation of enhancing body itself, with anti-aging.Therefore, the nutrition and health care of biologically active peptide
Effect has turned into the emphasis of domestic and foreign scholars subject study.Qiu Juan et al. pass through 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 be probably wherein to be 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.
The research on biologically active polypeptide has much at present, for example Chinese patent CN105254738A discloses one kind and come
The milk-derived biologically active polypeptide DELQDKIH of beta-casein is come from, Chinese patent CN105254739A discloses one kind and derived from
The milk-derived biologically active polypeptide GTQYTD of α s1- caseins, Chinese patent CN105254740A, which are disclosed, a kind of derives from α s2-
The milk-derived biologically active polypeptide NQFYQKF of casein.
The content of the invention
It is an object of the invention to provide a kind of biologically active polypeptide VPITPTLNR and its preparation method and application.
The purpose of the present invention can be achieved through the following technical solutions：
First aspect present invention, there is provided a kind of biologically active polypeptide VPITPTLNR, its amino acid sequence are Val-Pro-
Ile-Thr-Pro-Thr-Leu-Asn-Arg, such as SEQ ID NO：Shown in 1.
Preferably, the biologically active polypeptide is milk-derived.α s2- caseins are derive specifically from, and are α s2- caseins
The amino acid residue that modification A is the 132nd~140.α s2- ss-casein variants A amino acid sequences such as SEQ ID NO：Shown in 3.
The amino acid sequence and corresponding nucleotides sequence of α s2- caseins are classified as existing technology, and coding for alpha s2- caseins become
The biologically active polypeptide VPITPTLNR of the nucleotide fragments energy encoding mature of the amino acids residues of body A the 132nd~140.
Preferably, the biologically active polypeptide has anti-oxidation function and anti-senescence function.
Second aspect of the present invention, there is provided encode the nucleotide fragments of the biologically active polypeptide VPITPTLNR, its sequence
For：5 '-gtt ccc att act ccc act ctg aac aga-3 ', such as SEQ ID NO：Shown in 2.
Third aspect present invention, there is provided the preparation method of the biologically active polypeptide VPITPTLNR, gene can be passed through
The method of engineering is artificial synthesized, can be directly obtained from dairy products by the method isolated and purified, can directly pass through chemistry
It is synthetically prepared.
Fourth aspect present invention, there is provided the biologically active polypeptide VPITPTLNR is being prepared with anti-oxidation function
Application in food, health products, medicine or cosmetics.
Fifth aspect present invention, there is provided the biologically active polypeptide VPITPTLNR is being prepared with anti-senescence function
Application in food, health products or medicine.
Sixth aspect present invention, there is provided the biologically active polypeptide VPITPTLNR is being prepared while had anti-oxidant work(
Can be with the application in the food, health products or medicine of anti-senescence function.
Specifically, biologically active polypeptide VPITPTLNR of the invention, which can be used for preparing, reduces free radical to skin wound
Harmful cosmetics, prepare there is anti-oxidant and/or anti-aging medicine；And due to the biologically active polypeptide of the present invention
Product after VPITPTLNR is degraded by intestines and stomach still has bioactivity, thus can be also used for preparing the food such as Yoghourt,
Oxidation-resisting health-care product, and the oral preparation that is used for have anti-oxidant and/or anti-aging medicine.
Seventh aspect present invention, there is provided a kind of oxidation resistant product, including the biologically active polypeptide VPITPTLNR or institute
State biologically active polypeptide VPITPTLNR derivative；Described oxidation resistant product include antioxidant food, antioxidant health-care product,
Anti-oxidation medicine or antioxidation cosmetic product；The derivative of the biologically active polypeptide VPITPTLNR, refers in biologically active polypeptide
On VPITPTLNR amino acid side groups, aminoterminal or c-terminus carry out hydroxylating, carboxylated, be carbonylated, methylate, second
Acylation, phosphorylation, esterification or glycosylation etc. are modified, obtained polypeptide derivative.
Eighth aspect present invention, there is provided a kind of anti-aging product, including the biologically active polypeptide VPITPTLNR or institute
State biologically active polypeptide VPITPTLNR derivative；Described anti-aging product include antisenility cistanche food, antisenescence health product or
Antiaging agent；The derivative of the biologically active polypeptide VPITPTLNR, refers to the ammonia in biologically active polypeptide VPITPTLNR
On base acid side-chain radical, aminoterminal or c-terminus carry out hydroxylating, carboxylated, be carbonylated, methylate, acetylation, phosphorylation, ester
The modification such as change or glycosylation, obtained polypeptide derivative.
Ninth aspect present invention, there is provided product a kind of while that there is anti-oxidation function and anti-senescence function, including institute
State biologically active polypeptide VPITPTLNR or described biologically active polypeptides VPITPTLNR derivative；With anti-oxidation function and resist
The product of aging function includes food, health products or medicine；The derivative of the biologically active polypeptide VPITPTLNR, refers to
On biologically active polypeptide VPITPTLNR amino acid side groups, aminoterminal or c-terminus carry out hydroxylating, carboxylated, carbonyl
Change, methylate, acetylation, phosphorylation, the modification such as esterification or glycosylation, obtained polypeptide derivative.
Biologically active polypeptide VPITPTLNR's of the present invention has the beneficial effect that：The milk-derived biologically active polypeptide of the present invention
VPITPTLNR has preferable antioxidation activity and activity of fighting against senium；On the one hand, biologically active polypeptide of the invention
VPITPTLNR has preferable antioxidation activity, free radical that can be in removing machine body, improves the quality of life；On the other hand,
Can improve the vigor of internal anti-peroxidation enzyme system, the function of enhancing body resistance external source sexual stimulus, so as to reduce organism aging process,
Aging and sick probability, to developing with anti-oxidation function, the food of anti-senescence function, health products and medicine with very heavy
The meaning wanted.
Brief description of the drawings
Fig. 1：Mass chromatography extraction figure (m/z=505.8033)；
Fig. 2：Mass-to-charge ratio is the second order mses figure of 505.8033 fragment；
Fig. 3：Mass-to-charge ratio is 505.8033 polypeptide az, by crack conditions；
Fig. 4：[DPPH] methanol standard curve；
Fig. 5：Tocopherol Trolox standard curves；
Fig. 6：Hydrogen peroxide (H2O2) acute experiment.
Embodiment
Before specific embodiments of the present invention are further described, 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 the term used in the embodiment of the present invention is specific specific in order to describe
Embodiment, the protection domain being not intended to be limiting of the invention.
When embodiment provides number range, it should be appreciated that except non-invention is otherwise noted, two ends of each number range
Any one numerical value can be selected between point and two end points.Unless otherwise defined, in the present invention all technologies for using and
Scientific terminology is identical with the meaning that those skilled in the art of the present technique are generally understood that.Except used in embodiment specific method, equipment,
Outside material, according to grasp of the those skilled in the art to prior art and the record of the present invention, it can also use and this
Any method, equipment and the material of the similar or equivalent prior art of method, equipment described in inventive embodiments, material come real
The existing present invention.
Unless otherwise indicated, disclosed in this invention experimental method, detection method, preparation method using this technology lead
Domain conventional molecular biology, biochemistry, chromatin Structure and analysis, analytical chemistry, cell culture, recombinant DNA technology and
The routine techniques of association area.These technologies existing perfect explanation in the prior art, for details, reference can be made to Sambrook etc.
MOLECULAR CLONING：A LABORATORY MANUAL, Second edition, Cold Spring Harbor
Laboratory Press, 1989 and Third edition, 2001；Ausubel etc., CURRENT PROTOCOLS IN
MOLECULAR BIOLOGY, John Wiley＆Sons, New York, 1987and 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.
The active peptide VPITPTLNR's of embodiment 1 is artificial synthesized
First, the synthesis of biologically active peptide
1. RINK resin 3g (substitution value 0.3mmol/g) are weighed in 150ml reactor, with 50ml dichloromethane
(DCM) soak.
2. after 2 hours, resin is washed with nitrogen-dimethylformamide (DMF) of 3 times of resin volumes, is then drained, so
It is repeated four times, resin is drained rear stand-by.
3. a certain amount of 20% piperidines (piperidines/DMF=1 is added into reactor:4,v:V), it is placed on decolorization swinging table and shakes
20min is shaken, the Fmoc blocking groups on resin are sloughed with this.Washed four times with the DMF of 3 times of resin volumes after having taken off protection,
Then drain.
4. take 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. weigh amino acid Val in right amount and 1- hydroxyls-benzene a pair of horses going side by side triazole (HOBT) is in right amount in 50ml centrifuge tube, addition
20ml DMF is dissolved, and then adds 3ml N, and N DICs (DIC) vibration shakes up 1min, treats that solution is clear
It is added to after clear in reactor, then reactor is placed in 30 DEG C of shaking table and reacted.
6. after 2 hours, with a certain amount of acetic anhydride end socket (acetic anhydride:DIEA:DCM=1:1:2,v:v:V) half an hour,
Then washed four times, drained stand-by with the DMF of 3 times of resin volumes.
7. a certain amount of 20% piperidines (piperidines/DMF=1 is added into reactor:4, v:V), it is placed on decolorization swinging table and shakes
20min is shaken, the Fmoc blocking groups on resin are sloughed with this.Washed four times with DMF after having taken off protection, then drained.
8. take 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 50ml centrifuge tube, 25ml DMF generals are added
It dissolves, and the DIC vibrations for then adding 2.5ml shake up 1min, are added to after solution clarification in reactor, then by reactor
It is placed in 30 DEG C of shaking table and reacts.
10. after 1 hour, taking a small amount of resin to detect, (each two drop of inspection A, inspection B, 100 DEG C of reactions are detected with ninhydrin method
1min), if resin is colourless, illustrate that reaction is complete；If resin has color, illustrate that condensation is incomplete, continue to react.
After 11. question response is complete, washs resin four times with DMF, then drain, a certain amount of 20% is added into reactor
Piperidines (piperidines/DMF=1:4,v:V), it is placed on decolorization swinging table and rocks 20min, the Fmoc protection groups on resin is sloughed with this
Group.Washed four times with DMF after having taken off protection, then drain whether detection protection sloughs.
12. amino acid Pro, Ile, Thr, Pro, Thr, Leu, Asn and Arg are connected successively according to step 9-11.
13. after last amino acid is connected, protection is sloughed, is washed four times with DMF, is then taken out resin with methanol
It is dry.Then with 95 cutting liquid (trifluoroacetic acids:1,2 dithioglycols:3, isopropyl base silane:Water=95:2:2:1, v:v:V) by polypeptide
Cut down from resin (every gram of resin adds 10ml cutting liquids), and with ice ether (cutting liquid：Ether=1:9,v:V) centrifugation is heavy
Drop four times.
So far, artificial synthesized biologically active peptide VPITPTLNR.
2nd, the confirmation of biologically active peptide
1) UPLC is analyzed
UPLC conditions are as follows：
Instrument：Waters ACQUITY UPLC ultra high efficiency liquid phase-electron spray-level Four bar-time of-flight mass spectrometer
Chromatographic column specification：BEH C18 chromatographic columns
Flow velocity：0.4mL/min
Temperature：50℃
Ultraviolet detection wavelength：210nm
Sample size：2μL
Gradient condition：A liquid：Water containing 0.1% formic acid (v/v), B liquid：Acetonitrile containing 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
Remove solvent temperature (DEG C)：350
Go solvent stream (L/hr)：700.0
Collision energy (eV)：4.0
Sweep time (sec)：0.25
Interior sweep time (sec)：0.02
According to above analysis method, using ultra high efficiency liquid phase-electron spray-level Four bar-flight time mass spectrum, to bioactivity
Peptide VPITPTLNR carries out chromatography and mass spectral analysis, and its mass chromatography extraction figure is as shown in figure 1, extract the two level matter at this peak
As shown in Figures 2 and 3, the polypeptide mass-to-charge ratio that can obtain this peak is 505.8033Da, and retention time is for spectrogram and az, by crack conditions
25.7min。
3) result
From the figure 3, it may be seen that situation about being broken according to az, by, calculates by Mascot software analysis, obtains mass-to-charge ratio
505.8033Da fragment sequence is Val-Pro-Ile-Thr-Pro-Thr-Leu-Asn-Arg (VPITPTLNR), is designated as SEQ
ID NO：1.The fragment and α s2- ss-casein variants A the 132nd~140 residue sequence is corresponding, α s2- casamino acids
The GenBank numberings of sequence are AAA30479.1, and sequence is shown in SEQ ID NO：3.
The antioxidation activity experiment of the biologically active peptide of embodiment 2
First, [DPPH] method measure biologically active peptide VPITPTLNR antioxidation activity in vitro
1. experiment reagent and instrument：
Reagent：1,1- diphenyl -2- trinitrophenyl-hydrazines (1,1-Diphenyl-2-picrylhydrazyl [DPPH]),
Japanese Wako companies production；Methanol, Shanghai traditional Chinese medicines company provide；The milk-derived biologically active polypeptide that embodiment 1 obtains
VPITPTLNR。
Key instrument：Sunrise ELIASAs, Austrian Tecan Products；96 porocyte culture plates, the U.S.
Millipore companies manufacture；Assay balance, Meitelei-tolido Products.
2. experimental method：
(1) 1mmol/L [DPPH] methanol solution
0.349mg [DPPH] is weighed with assay balance to be dissolved in 1mL methanol solutions, prepares obtained 1mmol/L
[DPPH] methanol solution, tinfoil are kept in dark place, i.e., with i.e. use.
(2) measure of [DPPH] methanol standard curve
100 μ L [DPPH] methanol standard curve samples are separately added into by table 1 in 96 orifice plates, are stored at room temperature 90min, are used
ELIASA detects light absorption value at 517nm.
[DPPH] methanol of table 1 calibration curve solution is prepared
According to experimental result, using Excel matched curves and regression equation is calculated, as a result sees Fig. 4 (regression equations：Y=-
0.192x+0.2271, R2=0.9991).The linear relationship of [DPPH] methanol standard curve is good, coefficient correlation 0.999,
Show that [DPPH] methanol standard curve preci-sion and accuracy meets testing requirements.In terms of result, absorbance with
[DPPH] content is in inverse relation, and [DPPH] content is fewer, and light absorption value is higher, i.e. the ability of sample removing free radical is got over
By force.
(3) [DPPH] method measure biologically active peptide VPITPTLNR antioxidation activity
1) sample sets：80 μ L concentration are added in 96 orifice plates for 1mmol/L [DPPH] methanol solution, by table 2 respectively to add
Enter the testing sample (VPITPTLNR), positive control 1 (2.5mg/mL Trolox), positive control 2 of 20 μ L various concentrations
(0.025mg/mL Trolox), and negative control (phytic acid)；
2) blank group：On same 96 orifice plate, to add 80 μ L concentration as 1mmol/L [DPPH] methanol solutions and 20 μ L
The sample of deionized water does blank control.
After detected sample is loaded, 90min is stored at room temperature, light absorption value is detected at 517nm with ELIASA.Under
Formula calculates free radical scavenging activity, and experimental result is shown in Table 2.
Formula：
Table 2 [DPPH] method determines the antioxidation activity result of biologically active polypeptide
From table 2 it can be seen that the Trolox as the 2.5mg/mL of positive control have under the same conditions it is most strong clear
Except the ability of free radical, free radical all in solution can be almost removed, is secondly 0.025mg/mL Trolox, phytic acid, work
Property polypeptide.Polypeptide VPITPTLNR removes [DPPH] free radical rate and is presented bell with change in concentration, is 2.5mg/mL in concentration
Place reaches peak, is 25.93%.
2nd, ABTS methods measure biologically active peptide VPITPTLNR antioxidant activity in vitro
1. experiment reagent and instrument：
TAC detection kit (Total Antioxidant Capacity Assay Kit with ABTS
Method), purchased from the green skies biotechnology company in Shanghai；ABTS solution, oxidizing agent solution, watermiscible vitamin E (Trolox solution)
(10mmol/L), the milk-derived biologically active polypeptide VPITPTLNR that embodiment 1 obtains.
Key instrument：Sunrise ELIASAs, Austrian Tecan Products；96 porocyte culture plates, the U.S.
Millipore companies manufacture；Assay balance, Meitelei-tolido Products.
2. experimental method：
(1) preparation of ABTS working solutions
According to TAC detection kit specification, by ABTS solution and ABTS oxidizing agent solutions 1:1 mixing, keeps away
Used after light storage 12-16h.The ABTS mother liquors prepared at room temperature deposit by lucifuge, stable in 2-3 days.It is before use, dilute with PBS
Release 38-42 times of ABTS working stocks so that after the absorbance of ABTS working solutions subtracts corresponding PBS blank controls, A734 be 0.7 ±
0.05, ABTS working solution tinfoil is kept in dark place, now with the current.
(2) the making measure of tocopherol (Trolox) standard curve curve
200 μ L ABTS working solutions are added in each detection hole of 96 orifice plates, by the requirement of table 3 in standard curve detection hole
Tocopherol (Trolox) solution that 10 μ L are diluted with PBS is added, 10 μ L PBS is added in blank control wells, gently mixes.Room temperature
After being incubated 4min, light absorption value is detected at 734nm.
The solution of the tocopherol of table 3 (Trolox) standard curve determination is prepared
Experimental result, with Excel fit regression curves and regression equation is drawn, as a result as shown in Figure 5.Trolox
Standard curve linear relationship is good, and its coefficient correlation reaches 0.998, and the degree of accuracy and accuracy for showing the standard curve all meet
Testing requirements, calculated available for subsequent result.It can be seen that well anti-is presented with light absorption value in Trolox standard curves
Than relation, the concentration of Trolox solution is higher, and its light absorption value under 734nm is lower, i.e. the Scavenging ability of institute's test sample product
It is stronger.
(3) ABTS methods measure biologically active polypeptide VPITPTLNR oxidation resistance
200 μ L ABTS working solutions are added in each detection hole of 96 orifice plates, adding 10 μ L in sample detection hole treats test sample
Product, 10 μ L PBS are added in blank control wells, are gently mixed.After being incubated at room temperature 4min, extinction is detected at 734nm with ELIASA
Value.The TAC of sample is calculated according to standard curve.TAC representation is with Trolox standard liquids
Concentration represent that calculate free radical scavenging activity according to the following formula, experimental result is shown in Table 4.
TAC (mmol/g)=CTrolox/CS
In formula：CTrolox--- with sample light absorption value identical Trolox concentration of standard solution (mmol/L)
CS--- the concentration (mg/mL) of synthesis polypeptide sample
The ABTS methods of table 4 measure biologically active polypeptide VPITPTLNR TAC result
Pass through TAC method (Total Antioxidant Capacity Assay Kit with ABTS methods)
Polypeptide VPITPTLNR external total antioxidant activity is determined, it is found that biologically active polypeptide VPITPTLNR compares blank
Its light absorption value decrease to some degree of group, there is the ability of preferable reduction-oxidation material.As shown in Table 4, polypeptide is found
VPITPTLNR TAC raises with the rise of peptide concentration, in the case of concentration is 5mg/mL, polypeptide
VPITPTLNR total antioxidation level reaches 0.1996mmol/g, i.e., under 5mg/m L concentration, its TAC with
1mmol/L Trolox TAC mutually maintains an equal level.Therefore, can assert the biologically active polypeptide VPITPTLNR of invention has
Significant oxidation resistance.
The activity of fighting against senium experiment of the biologically active peptide of embodiment 3
First, biologically active polypeptide VPITPTLNR improves the experiment of drosophila survival ability
1. experiment reagent and instrument：
Reagent：Oregon K wild type Drosophila melanogasters, agricultural college of Shanghai Communications University genetics experiments room；Agar powder, state
Chemical reagent Co., Ltd of medicine group；The milk-derived biologically active polypeptide VPITPTLNR that embodiment 1 obtains.
Instrument and equipment：The ultra-clean water of CM-230 types mole, Shanghai Moller scientific instrument Co., Ltd；G136T type Zealway intelligence
Energy high-temperature sterilization pot, Xiamen Zhi Wei instruments Science and Technology Ltd.；BJ-CD SERIES bio-incubators, Shanghai is rich to prove to be true after interrogation industry public affairs
Department；GRX-9073 type hot air sterilizers, one permanent Science and Technology Ltd. of Shanghai.
2. experimental method：
Using drosophila as experimental model：The drosophila adult newly to sprout wings in 8 hours is collected, male and female random transferring is divided after anesthesia to respectively
In experimental group, every group of each sex 100, every group of setting 3 is parallel, and control group gives conventional corn powder culture medium, experimental group
VPITPTLNR biologically active peptides-corn culture medium respectively containing 0.05mg/ml, 0.5mg/ml, 1mg/ml.Change within every 2 days
Fresh culture once, is observed and records the death toll of different sexes drosophila daily, untill drosophila is all dead.Draw fruit
Fly survivorship curve, and calculate the average life span of different sexes drosophila and maximum life span (takes 5 drosophilas of last death to be united
Meter).
3. experimental result and analysis：
Influence situations of the table 5-1 VPITPTLNR to the Male Drosophila life-span
It was found from from table 5-1, relative to blank control group, low dose group Male Drosophila average life span does not have significant change,
But middle dose group and advanced amount group Male Drosophila average life span are improved, respectively 16.01% and 9.73%, but only middle dosage
Group generates significant difference (p<0.05), illustrate that the average life span conspicuousness of middle dose group Male Drosophila improves.Meanwhile middle dose
The half death time of amount group and high dose group drosophila is improved, but does not have notable difference in terms of MaLS.By table
5-2 understands that female Drosophila low dose group, middle dose group and high dose group increase in terms of average life span, but do not produce
Raw significant difference.But the MaLS of middle dose group and high dose group increases, extend 7 days respectively compared with blank control group
With 6 days, and generate significant difference (P<0.05).
This experimental result illustrates that biologically active polypeptide VPITPTLNR can improve the average longevity of drosophila under finite concentration
Life and MaLS, but it is relevant with concentration and sex.This phenomenon related to tested material concentration, strain be probably because
VPITPTLNR participates in the part biological metabolism of drosophila, or the antioxidant system organized by improving drosophila extends to reach
The effect of life span of drosophila melanogaster.Because the metabolism of different lines drosophila can have any different, so as to cause the difference of result.And the difference of sex
It is different, it may be possible to because female Drosophila inherently has certain conservative and the resistance to external environment, so VPITPTLNR
To female Drosophila life and unobvious.
2nd, biologically active polypeptide VPITPTLNR hydrogen peroxide Acute oxidative is tested
1. experiment reagent and instrument：
Reagent：Oregon K wild type Drosophila melanogasters, agricultural college of Shanghai Communications University genetics experiments room；Agar powder, state
Chemical reagent Co., Ltd of medicine group；Hydrogen peroxide, Shanghai Ling Feng chemical reagent Co., Ltd；The milk-derived that embodiment 1 obtains
Biologically active polypeptide VPITPTLNR.
Instrument and equipment：The ultra-clean water of CM-230 types mole, Shanghai Moller scientific instrument Co., Ltd；Mi Libo Millipore
MILLEX GP0.22 μm filter membranes, Millipore Corp. of the U.S.；GL-22M high speed freezing centrifuges, Shanghai Lu Xiang instrument centrifuge instruments
Co., Ltd.
2. experimental method：
The drosophila adult newly to sprout wings in 8 hours is collected, male and female random transferring is divided after anesthesia into each experimental group, takes the life-span real
The preferable peptide concentration culture medium of middle result is tested, sets blank control group and experimental group, control group to give conventional corn powder culture medium.
Every group of male and female sex drosophila is 50, and drosophila is cultivated three weeks.Then 5 males and 5 female Drosophilas are taken to be transferred to every time
Contain a papery disk in one new container, in new container, disk contain 300 μ L concentration for 5% sucrose solution with
And concentration is 30% hydrogen peroxide 1ml, blank group and experimental group are exposed to toxicity peroxide caused by this hydrogen peroxide
In environment, 10 Duplicate Samples of every group of setting, its oxidation resistance is observed.Every 4 hour record drosophila The dead quantity and sex, until
Drosophila is all dead.
3. experimental result and analysis：
From Fig. 6 (A) as can be seen that for Male Drosophila, after VPITPTLNR feedings, in Each point in time, male
The survival rate of drosophila is above the drosophila without VPITPTLNR feedings, and the time-to-live increases compared with blank control group, explanation
After feeding VPITPTLNR, Male Drosophila oxidation resistance increases.In Fig. 6 (B), feeding VPITPTLNR female Drosophila,
Survival rate is obvious high in 15h in the hydrogen peroxide environment of high concentration and control group, illustrates that this period female Drosophila is anti-oxidant
Ability increases.But later experiments group and control group survival curve essentially coincide, and illustrate feeding VPITPTLNR female Drosophila
Oxidation resistance gradually weaken, there is no difference with control group after certain time.This test result indicates that, VPITPTLNR
The oxidation resistance of drosophila can be improved.According to H2O2Acute toxicity testing result, it can speculate that VPITPTLNR may pass through tune
Cat catalase activity is saved to improve drosophila to H2O2The resistivity of damage.
3rd, the experiment that biologically active polypeptide VPITPTLNR influences on drosophila SOD and MAD content
1. experiment reagent and instrument：
Reagent：Oregon K wild type Drosophila melanogasters, agricultural college of Shanghai Communications University genetics experiments room；Agar powder, state
Chemical reagent Co., Ltd of medicine group；MDA MDA kits, Science and Technology Ltd. of Nanjing Keygen Biotech；SOD super oxygens
Compound is disproportionated enzyme reagent kit, and bio tech ltd is built up in Nanjing；The milk-derived biologically active polypeptide that embodiment 1 obtains
VPITPTLNR。
Instrument and equipment：The ultra-clean water of CM-230 types mole, Shanghai Moller scientific instrument Co., Ltd；Organize homogenizer, Shanghai
Member is as bio tech ltd；G136T type Zealway intelligence high-temperature sterilization pots, Xiamen Zhi Wei instruments Science and Technology Ltd.；
BJ-CD SERIES bio-incubators, Shanghai Bo Xun industrial corporations；GRX-9073 type hot air sterilizers, one permanent science and technology of Shanghai have
Limit company；Infinite type ELIASAs, Austrian Di Ken Co., Ltds.
2. experimental method：
The drosophila adult newly to sprout wings in 8 hours is collected, male and female random transferring is divided after anesthesia into each experimental group, every group each
Sex 100, every group of setting 3 is parallel, and control group gives conventional corn powder culture medium, and experimental group is respectively to contain 0.05mg/
Ml, 0.5mg/ml, 1mg/ml VPITPTLNR biologically active peptides-corn culture medium.Change fresh culture once within every 2 days, raise
After supporting 30 days, every group weighs drosophila 40mg, adds 0.5ml physiological saline, and homogenate is ground in ice bath, the interval 10s seconds, is repeated
3 times, homogenate is made, every group of drosophila SOD activity and MDA levels are determined according to kit explanation.Utilize MDA detection kits
The levels of the lipid peroxidation product MDA in drosophila body are detected, the wavelength of spectrophotometer is 532nm.
3. experimental result and analysis：
Influences of the VPITPTLNR of table 6 to drosophila SOD, MDA
As can be known from Table 6, relative to blank control group, the SOD contents in the female male drosophila body of polypeptide treatment group are improved,
And for Male Drosophila group, when peptide concentration reaches 1mg/ml, there is significant difference in the SOD contents in drosophila body, and
Then there is significant difference when peptide concentration is 0.5mg/ml and 1mg/ml in female Drosophila group.Illustrate by taking in certain polypeptide,
Internal SOD contents can be improved, and help body protective itself to prevent oxidative damage.MDA contents can see from table 6,
MDA contents in experimental group Male Drosophila and female Drosophila body have reduction.Relative to male blank control group MDA contents 1.37
± 0.21 μm of ol/L, there is the reduction of conspicuousness for the MDA contents of 0.5mg/ml and 1mg/ml drosophila groups in concentration, and female Drosophila
In group, when 1mg/ml peptides are handled, there is the reduction of conspicuousness in the MDA contents in drosophila body.Because MDA is body lipid peroxide
Change and generate, the reduction of its content illustrates that the Antioxidant Enzymes vigor of drosophila is improved indirectly, so as to protect body
Histoorgan will not produce a large amount of MDAs.
From experimental result as can be seen that SOD and MDA experimental result is mutually proved, it may be said that gelatine/biological activity polypeptide
VPITPTLNR is favorably improved the vigor of the Antioxidant Enzymes in body body, so as to effectively improve the oxidation resistance of body,
Reduce body is stimulated by the bad factor, so as to reduce organism aging process, aging and sick probability, all in all, for male fruit
The effect of fly is better than female Drosophila.
The above-mentioned description to embodiment is understood that for ease of those skilled in the art and using invention.
Person skilled in the art obviously can easily make various modifications to these embodiments, and described herein general
Principle is applied in other embodiment without by performing creative labour.Therefore, the invention is not restricted to above-described embodiment, ability
Field technique personnel do not depart from improvement that scope made and modification all should be the present invention's according to the announcement of the present invention
Within protection domain.
Sequence table
<110>Zhejiang Hui Tai life and healths Science and Technology Ltd.；Shanghai Bo Hui bio tech ltd
<120>A kind of biologically active polypeptide VPITPTLNR and its preparation method and application
<160> 3
<170> SIPOSequenceListing 1.0
<210> 1
<211> 9
<212> PRT
<213>Artificial sequence (Artificial Sequence)
<400> 1
Val Pro Ile Thr Pro Thr Leu Asn Arg
1 5
<210> 2
<211> 27
<212> DNA
<213>Artificial sequence (Artificial Sequence)
<400> 2
gttcccatta ctcccactct gaacaga 27
<210> 3
<211> 222
<212> PRT
<213>Artificial sequence (Artificial Sequence)
<400> 3
Met Lys Phe Phe Ile Phe Thr Cys Leu Leu Ala Val Ala Leu Ala Lys
1 5 10 15
Asn Thr Met Glu His Val Ser Ser Ser Glu Glu Ser Ile Ile Ser Gln
20 25 30
Glu Thr Tyr Lys Gln Glu Lys Asn Met Ala Ile Asn Pro Ser Lys Glu
35 40 45
Asn Leu Cys Ser Thr Phe Cys Lys Glu Val Val Arg Asn Ala Asn Glu
50 55 60
Glu Glu Tyr Ser Ile Gly Ser Ser Ser Glu Glu Ser Ala Glu Val Ala
65 70 75 80
Thr Glu Glu Val Lys Ile Thr Val Asp Asp Lys His Tyr Gln Lys Ala
85 90 95
Leu Asn Glu Ile Asn Gln Phe Tyr Gln Lys Phe Pro Gln Tyr Leu Gln
100 105 110
Tyr Leu Tyr Gln Gly Pro Ile Val Leu Asn Pro Trp Asp Gln Val Lys
115 120 125
Arg Asn Ala Val Pro Ile Thr Pro Thr Leu Asn Arg Glu Gln Leu Ser
130 135 140
Thr Ser Glu Glu Asn Ser Lys Lys Thr Val Asp Met Glu Ser Thr Glu
145 150 155 160
Val Phe Thr Lys Lys Thr Lys Leu Thr Glu Glu Glu Lys Asn Arg Leu
165 170 175
Asn Phe Leu Lys Lys Ile Ser Gln Arg Tyr Gln Lys Phe Ala Leu Pro
180 185 190
Gln Tyr Leu Lys Thr Val Tyr Gln His Gln Lys Ala Met Lys Pro Trp
195 200 205
Ile Gln Pro Lys Thr Lys Val Ile Pro Tyr Val Arg Tyr Leu
210 215 220
Claims (10)
1. a kind of biologically active polypeptide VPITPTLNR, it is characterised in that its amino acid sequence is Val-Pro-Ile-Thr-Pro-
Thr-Leu-Asn-Arg。
2. a kind of biologically active polypeptide VPITPTLNR according to claim 1, it is characterised in that the bioactivity is more
Peptide is milk-derived.
3. encode the nucleotide fragments of biologically active polypeptide VPITPTLNR described in claim 1, it is characterised in that the nucleosides
The sequence of acid fragment such as SEQ ID NO：Shown in 2.
4. biologically active polypeptide VPITPTLNR as claimed in claim 1 preparation method, it is characterised in that pass through genetic engineering
Method it is artificial synthesized, or directly obtained from dairy products by the method isolated and purified, or directly prepared by chemical synthesis.
5. biologically active polypeptide VPITPTLNR as claimed in claim 1 application, it is characterised in that the biologically active polypeptide
Applications of the VPITPTLNR in the food with anti-oxidation function, health products, medicine or cosmetics are prepared.
6. biologically active polypeptide VPITPTLNR as claimed in claim 1 application, it is characterised in that the biologically active polypeptide
Applications of the VPITPTLNR in the food with anti-senescence function, health products or medicine is prepared.
7. biologically active polypeptide VPITPTLNR as claimed in claim 1 application, it is characterised in that the biologically active polypeptide
Applications of the VPITPTLNR in the food with anti-oxidation function and anti-senescence function, health products or medicine is prepared.
8. a kind of oxidation resistant product, it is characterised in that including biologically active polypeptide VPITPTLNR as claimed in claim 1 or institute
State biologically active polypeptide VPITPTLNR derivative；Described oxidation resistant product include antioxidant food, antioxidant health-care product,
Anti-oxidation medicine or antioxidation cosmetic product；The derivative of the biologically active polypeptide VPITPTLNR, refers in biologically active polypeptide
On VPITPTLNR amino acid side groups, aminoterminal or c-terminus carry out hydroxylating, carboxylated, be carbonylated, methylate, second
Acylation, phosphorylation, esterification or glycosylation modified, obtained polypeptide derivative.
9. a kind of anti-aging product, it is characterised in that including biologically active polypeptide VPITPTLNR as claimed in claim 1 or institute
State biologically active polypeptide VPITPTLNR derivative；Described anti-aging product include antisenility cistanche food, antisenescence health product or
Antiaging agent；The derivative of the biologically active polypeptide VPITPTLNR, refers to the ammonia in biologically active polypeptide VPITPTLNR
On base acid side-chain radical, aminoterminal or c-terminus carry out hydroxylating, carboxylated, be carbonylated, methylate, acetylation, phosphorylation, ester
Change or glycosylation modified, obtained polypeptide derivative.
10. a kind of product with anti-oxidation function and anti-senescence function, it is characterised in that including raw as claimed in claim 1
Thing active peptides VPITPTLNR or described biologically active polypeptides VPITPTLNR derivative；With anti-oxidation function and anti-aging
The product of function includes food, health products or medicine；The derivative of the biologically active polypeptide VPITPTLNR, refers in biology
On active peptides VPITPTLNR amino acid side groups, aminoterminal or c-terminus carry out hydroxylating, carboxylated, carbonylation, first
Base, acetylation, phosphorylation, esterification or glycosylation modified, obtained polypeptide derivative.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201711310260.9A CN107880105B (en) | 2017-12-11 | 2017-12-11 | Bioactive polypeptide VPITPTLNR, and preparation method and application thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201711310260.9A CN107880105B (en) | 2017-12-11 | 2017-12-11 | Bioactive polypeptide VPITPTLNR, and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
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| CN107880105B CN107880105B (en) | 2020-06-16 |
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ID=61773497
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| Application Number | Title | Priority Date | Filing Date |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1374885A1 (en) * | 2002-06-27 | 2004-01-02 | Ingredia | Use of at least one peptide of alpha-s2 casein with inhibiting activity of ACE for the preparation of medicaments and foodstuffs |
| WO2005081628A2 (en) * | 2004-03-01 | 2005-09-09 | Peptera Pharmaceutical Ltd. | Casein derived peptides and therapeutic uses thereof |
| CN106146644A (en) * | 2016-09-07 | 2016-11-23 | 哈尔滨工业大学 | Antithrombotic peptide and directional enzymatic preparation method thereof |
-
2017
- 2017-12-11 CN CN201711310260.9A patent/CN107880105B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1374885A1 (en) * | 2002-06-27 | 2004-01-02 | Ingredia | Use of at least one peptide of alpha-s2 casein with inhibiting activity of ACE for the preparation of medicaments and foodstuffs |
| WO2005081628A2 (en) * | 2004-03-01 | 2005-09-09 | Peptera Pharmaceutical Ltd. | Casein derived peptides and therapeutic uses thereof |
| CN106146644A (en) * | 2016-09-07 | 2016-11-23 | 哈尔滨工业大学 | Antithrombotic peptide and directional enzymatic preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| GEMMA PUJADAS等: "The dipeptidyl peptidase-4 (DPP-4) inhibitor teneligliptin functions as antioxidant on human endothelial cells exposed to chronic hyperglycemia and metabolic high-glucose memory", 《ENDOCRINE》 * |
| HIROSHI UENISHI等: "Isolation and identification of casein-derived dipeptidyl-peptidase 4 (DPP-4)-inhibitory peptide LPQNIPPL from gouda-type cheese and its effect on plasma glucose in rats", 《INTERNATIONAL DAIRY JOURNAL》 * |
| J. C. RODRÍGUEZ-FIGUEROA等: "Novel angiotensin I-converting enzyme inhibitory peptides produced in fermented milk by specific wild Lactococcus lactis strains", 《J. DAIRY SCI.》 * |
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| CN107880105B (en) | 2020-06-16 |
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