CN109160944A - A kind of biologically active polypeptide ATAVPIIFF and its preparation method and application - Google Patents
A kind of biologically active polypeptide ATAVPIIFF and its preparation method and application Download PDFInfo
- Publication number
- CN109160944A CN109160944A CN201811002919.9A CN201811002919A CN109160944A CN 109160944 A CN109160944 A CN 109160944A CN 201811002919 A CN201811002919 A CN 201811002919A CN 109160944 A CN109160944 A CN 109160944A
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- Prior art keywords
- atavpiiff
- biologically active
- active polypeptide
- polypeptide
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- JIODCDXKCJRMEH-NHCYSSNCSA-N Val-Arg-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N JIODCDXKCJRMEH-NHCYSSNCSA-N 0.000 description 1
- PAPWZOJOLKZEFR-AVGNSLFASA-N Val-Arg-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O)N PAPWZOJOLKZEFR-AVGNSLFASA-N 0.000 description 1
- XLDYBRXERHITNH-QSFUFRPTSA-N Val-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)C(C)C XLDYBRXERHITNH-QSFUFRPTSA-N 0.000 description 1
- OTJMMKPMLUNTQT-AVGNSLFASA-N Val-Leu-Arg Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](C(C)C)N OTJMMKPMLUNTQT-AVGNSLFASA-N 0.000 description 1
- UMPVMAYCLYMYGA-ONGXEEELSA-N Val-Leu-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O UMPVMAYCLYMYGA-ONGXEEELSA-N 0.000 description 1
- JAIZPWVHPQRYOU-ZJDVBMNYSA-N Val-Thr-Thr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](C(C)C)N)O JAIZPWVHPQRYOU-ZJDVBMNYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
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- 238000002835 absorbance Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 108010044940 alanylglutamine Proteins 0.000 description 1
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 1
- 230000002605 anti-dotal effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 108010013835 arginine glutamate Proteins 0.000 description 1
- 108010062796 arginyllysine Proteins 0.000 description 1
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- 230000008033 biological extinction Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 210000003022 colostrum Anatomy 0.000 description 1
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- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 1
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- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 1
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 1
- 108010072405 glycyl-aspartyl-glycine Proteins 0.000 description 1
- 108010045126 glycyl-tyrosyl-glycine Proteins 0.000 description 1
- 108010015792 glycyllysine Proteins 0.000 description 1
- 108010087823 glycyltyrosine Proteins 0.000 description 1
- 108010092114 histidylphenylalanine Proteins 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 229940088592 immunologic factor Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
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- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
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- 150000002632 lipids Chemical class 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 108010003700 lysyl aspartic acid Proteins 0.000 description 1
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- 108010054155 lysyllysine Proteins 0.000 description 1
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- 238000004949 mass spectrometry Methods 0.000 description 1
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- 235000010755 mineral Nutrition 0.000 description 1
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- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000003399 opiate peptide Substances 0.000 description 1
- 238000000399 optical microscopy Methods 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
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- 229940055695 pancreatin Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 238000005502 peroxidation Methods 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
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- 230000009758 senescence Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 108010026333 seryl-proline Proteins 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
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- 108010061238 threonyl-glycine Proteins 0.000 description 1
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- 210000001519 tissue Anatomy 0.000 description 1
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- 150000003852 triazoles Chemical class 0.000 description 1
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- 108010003137 tyrosyltyrosine Proteins 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 108010030651 valyl-glutamyl-prolyl-isoleucyl-prolyl-tyrosine Proteins 0.000 description 1
- 108010073969 valyllysine Proteins 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
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- 235000021247 β-casein Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/335—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Lactobacillus (G)
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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
-
- 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
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Chemical & Material Sciences (AREA)
- Biophysics (AREA)
- Food Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Nutrition Science (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Polymers & Plastics (AREA)
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- Birds (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
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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 ATAVPIIFF and its preparation method and application, its amino acid sequence of biologically active polypeptide ATAVPIIFF are Ala-Thr-Ala-Val-Pro-Ile-Ile-Phe-Phe.By the experiment of ion vitro immunization function point analysis, internal Antisenility Experiment, polypeptide A TAVPIIFF is demonstrated with preferable immunoloregulation function and activity of fighting against senium, on the one hand, biologically active polypeptide ATAVPIIFF of the invention can enhance the in-vitro multiplication ability of lymphocyte and macrophage, the ability that body resists extraneous pathogenic infection is improved, body disease incidence is reduced；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 immunoloregulation 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 field, more particularly, to a kind of biologically active polypeptide ATAVPIIFF and preparation method thereof and
Using.
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.
Immune-active peptides are to obtain and prove that one kind biology of its physiological activity is living from cream for the first time after opioid peptides discovery
Property polypeptide.Jolles in 1981 et al. has found for the first time, using trypsin hydrolysis people lactoprotein, an available amino acid sequence
It is classified as the hexapeptide of Val-Glu-Pro-Ile-Pro-Tyr, experiment in vitro proves that the peptide can enhance Turnover of Mouse Peritoneal Macrophages pair
The phagocytosis of sheep red blood cell (SRBC).Migliore-Samour et al. has found the hexapeptide Thr-Thr-Met-Pro- from casein
Leu-Trp can stimulate sheep erythrocyte to the phagocytosis of mouse peritoneal macrophages and enhancing for kerekou pneumonia primary
The resistance of bacterium.Newborn source immunomodulatory peptides (PGPIPN) the feeding rat of Li Su duckweed et al. synthesis finds rat peritoneal macrophages
Phagocytosis and the relevant immunoloregulation function of red blood cell have significant enhancing.
Studies have shown that immune-active peptides can not only enhance immunity of organisms, the proliferation of body lymphocyte, enhancing are stimulated
The phagocytic function of macrophage promotes the release of cell factor, improves the ability that body resists extraneous pathogenic infection, reduces machine
Body disease incidence, and the immunological rejection of body will not be caused.
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 ATAVPIIFF 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 ATAVPIIFF, amino acid sequence Ala-Thr-
Ala-Val-Pro-Ile-Ile-Phe-Phe, as shown in SEQ ID NO:1.
Preferably, the biologically active polypeptide derives from Lactobacillus helveticus mycoprotein.It is derive specifically from LBH_0027 |
m.24LBH_0027|g.24ORF LBH_0027|g.24LBH_0027|m.24type:5prime_partial len:320(+)
LBH_0027:1-960 (+) albumen, and the 17th~25, albumen amino acid residue thus.LBH_0027|m.24LBH_
0027|g.24ORF LBH_0027|g.24LBH_0027|m.24type:5prime_partial len:320(+)LBH_
0027:1-960 (+) protein amino acid sequence is as shown in SEQ ID NO:3.
LBH_0027|m.24LBH_0027|g.24ORF LBH_0027|g.24LBH_0027|m.24type:5prime_
The amino acid sequence and corresponding nucleotides sequence of partial len:320 (+) LBH_0027:1-960 (+) albumen are classified as existing
Technology encodes the biologically active polypeptide of the nucleotide fragments energy encoding mature of this 17th~25 amino acids residue of albumen
ATAVPIIFF。
Preferably, the biologically active polypeptide has immunoloregulation function and anti-senescence function.
Second aspect of the present invention provides the nucleotide fragments for encoding the biologically active polypeptide ATAVPIIFF, sequence
Are as follows: 5 '-cta ctg ctg ttc cta tta tat ttt ttg-3 ', as shown in SEQ ID NO:2.
Third aspect present invention provides the preparation method of the biologically active polypeptide ATAVPIIFF, can pass through gene
The method of engineering is artificial synthesized, can directly obtain from Lactobacillus helveticus thallus by the method that clasmatosis isolates and purifies, can
Directly to be prepared by chemical synthesis.
Fourth aspect present invention, providing the biologically active polypeptide ATAVPIIFF in preparation has immunoloregulation function
Food, health care product, the application in drug or cosmetics.
Fifth aspect present invention, providing the biologically active polypeptide ATAVPIIFF in preparation has anti-senescence function
Application in food, health care product or drug.
Sixth aspect present invention provides the biologically active polypeptide ATAVPIIFF in preparation while having immunological regulation
Application in the food of function and anti-senescence function, health care product or drug.
Specifically, biologically active polypeptide ATAVPIIFF of the invention, which can be used for preparing, reduces free radical to skin wound
The harmful drug of cosmetics, preparation with immunological regulation and/or anti-aging；And due to biologically active polypeptide of the invention
Product after ATAVPIIFF is degraded by gastrointestinal tract still has bioactivity, thus can be also used for preparing the food such as Yoghourt,
Adjust the health care product of immunity, and the oral drug being used to prepare with immunological regulation and/or anti-aging.
Seventh aspect present invention, provides a kind of immunological regulation product, including the biologically active polypeptide ATAVPIIFF or
The derivative of the biologically active polypeptide ATAVPIIFF；The immunological regulation product includes immunological regulation food, immunological regulation
Health care product, immunoregulation medicament or immunological regulation cosmetics；The derivative of the biologically active polypeptide ATAVPIIFF, refers to
On the amino acid side groups of biologically active polypeptide ATAVPIIFF, aminoterminal or c-terminus carry out hydroxylating, carboxylated, carbonyl
The modification such as change, methylation, acetylation, phosphorylation, esterification or glycosylation, obtained polypeptide derivative.
Eighth aspect present invention provides a kind of anti-aging product, including the biologically active polypeptide ATAVPIIFF or institute
State the derivative of biologically active polypeptide ATAVPIIFF；The anti-aging product include antisenility cistanche food, antisenescence health product or
Antiaging agent；The derivative of the biologically active polypeptide ATAVPIIFF, refers to the ammonia in biologically active polypeptide ATAVPIIFF
On base acid side-chain radical, aminoterminal or c-terminus carry out hydroxylating, carboxylated, carbonylation, methylation, acetylation, phosphorylation, ester
The modification such as change or glycosylation, obtained polypeptide derivative.
Ninth aspect present invention provides product that is a kind of while having immunoloregulation function and anti-senescence function, including
The derivative of the biologically active polypeptide ATAVPIIFF or the biologically active polypeptide ATAVPIIFF；With immunoloregulation function
Product with anti-senescence function includes food, health care product or drug；The derivative of the biologically active polypeptide ATAVPIIFF is
Refer on the amino acid side groups of biologically active polypeptide ATAVPIIFF, aminoterminal or c-terminus carry out hydroxylating, carboxylated,
The modification such as carbonylation, methylation, acetylation, phosphorylation, esterification or glycosylation, obtained polypeptide derivative.
Biologically active polypeptide ATAVPIIFF's of the present invention has the beneficial effect that biologically active polypeptide ATAVPIIFF of the invention
Immunity of organisms activity and activity of fighting against senium are adjusted with preferable；On the one hand, biologically active polypeptide ATAVPIIFF of the invention
The in-vitro multiplication ability of lymphocyte and macrophage can be enhanced, improve the ability that body resists extraneous pathogenic infection, drop
Low body disease incidence；On the other hand, it can be improved the vigor of internal anti-peroxidation enzyme system, enhancing body resists external source sexual stimulus
Function has the cream of immunoloregulation function and anti-senescence function to exploitation to reduce organism aging process, aging and sick probability
Product and health care product have a very important significance.
Detailed description of the invention
Fig. 1: mass chromatography extracts figure (m/z=978.5601)；
Fig. 2: the second order ms figure for the segment that mass-to-charge ratio is 978.5601；
Fig. 3: polypeptide az, by crack conditions that mass-to-charge ratio is 978.5601；
Fig. 4: 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. 5: each group mice serum IL-6 variation table；
Fig. 6: each group mice serum TNF-α changes table；
Fig. 7: each group mice serum IL-2 variation table；
Fig. 8: each group mice serum IL-10 variation 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, 1989 and 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 ATAVPIIFF'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 Ala 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 Thr, Ala, Val, Pro, Ile, Ile, Phe and Phe 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 ATAVPIIFF.
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 ATAVPIIFF carries out chromatography and mass spectral analysis, and mass chromatography extraction figure is as shown in Figure 1, extract the second level matter at this peak
Spectrogram 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 978.5601Da, and retention time is
47.6min。
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 978.5601Da is Ala-Thr-Ala-Val-Pro-Ile-Ile-Phe-Phe (ATAVPIIFF), is denoted as SEQ
ID NO:1.The segment and LBH_0027 | m.24 LBH_0027 | g.24 ORF LBH_0027 | g.24LBH_0027 | m.24
The residue sequence of type:5prime_partial len:320 (+) LBH_0027:1-960 (+) the 17th~25, albumen is opposite
It answers, sequence is shown in SEQ ID NO:3.
The adjusting immunity of organisms activity experiment of 2 biologically active peptide of embodiment
One, the vitro lymphocyte proliferation capacity experimental of mtt assay measurement biologically active polypeptide ATAVPIIFF
1. experimental material and instrument:
Reagent and material: experimental animal balb/c mouse (male 6-8 week old, Shanghai Communications University's agricultural and biological institute
Animal experimental center)；The biologically active polypeptide ATAVPIIFF that embodiment 1 obtains；Mouse lymphocyte extracting solution (is purchased from rope
Precious company)；RPMI1640 culture medium (is purchased from GIBCO company)；3- (4,5- dimethylthiazole -2) -2,5- diphenyltetrazolium bromide bromine
Salt (MTT is purchased from Amresco company)；ConA (ConA is purchased from Sigma company)；(BSA is purchased from bovine serum albumin(BSA)
Genebase company)；Pepsin (is purchased from Sigma company)；Pancreatin (Corolase PP is purchased from AB company).
Instrument and equipment: LRH-250F biochemical cultivation case, Shanghai perseverance Science and Technology Ltd.；GL-22M high speed freezing centrifuge,
Shanghai Lu Xiang instrument centrifuge Instrument Ltd.；150 CO2 incubator of Hera cell, Heraeus company；Dragon
Wellscan MK3 microplate reader, Labsystems company；ALPHA 1-2-LD vacuum freeze drier, Christ company；Superelevation
Effect liquid phase chromatogram-quadrupole rod time of-flight mass spectrometer, waters company.
2. experimental method:
Mouse spleen is taken under aseptic condition, mouse lymphocyte is extracted with lymphocyte extracting solution, carries out Yuan Dynasty's culture.With
Cell density is adjusted to 2.5 × 10 by complete RPMI1640 culture solution6A/mL.It is sequentially added in 96 porocyte culture plates:
100 μ L mouse lymphocyte suspensions, 100 μ L RPMI1640 complete culture solutions, 20 μ L ConAs, 100 μ L samples.In addition,
Blank control group (PBS of pH7.2~7.4,3mol/L) and negative control group (500 μ g/mL BSA) are set, research shows that its is right
It is not influenced in vitro lymphocyte proliferation.Every group of 3 parallel laboratory test samples.In 5%CO2After cultivating 68h in 37 DEG C of incubators,
20 μ L MTT are added in every hole under aseptic condition, continue to cultivate 4h, carefully discard supernatant liquid, and 100 μ L dimethyl sulfoxides are added in every hole,
37 DEG C of biochemical cultivation cases hatch 10min, shake up, measure light absorption value at 570nm with microplate reader.
Vitro lymphocyte proliferation ability indicates that calculation method is as follows with stimulus index:
In formula: A1For blank control at the 570nm under light absorption value；A2For negative control group at the 570nm under extinction
Value, A3For experimental group at the 570nm under light absorption value.
3. experimental result and analysis:
Influence of the 1 biologically active polypeptide ATAVPIIFF of table to vitro lymphocyte proliferation
| Experimental group | Stimulus index SI |
| Negative control group | 1 |
| ATAVPIIFF | 1.175±0.021* |
Note: * labelled notation is to have significant difference (P < 0.05) compared with negative control.
Experimental result is shown in Table 1.As shown in Table 1, in the item that the mass concentration of biologically active peptide ATAVPIIFF is 100 μ g/mL
Under part, the stimulus index of biologically active peptide ATAVPIIFF is greater than BSA, illustrates ATAVPIIFF to a certain extent and can stimulate and is external small
The proliferation of mouse lymphotactin.And the stimulus index of ATAVPIIFF reached 1.175 and negative control group have significant difference
(P<0.05).Therefore, it can be assumed that active peptides ATAVPIIFF has the ability for remarkably promoting mouse lymphocyte proliferation,
It can be used as a kind of health care product or additive be edible, can be improved the immunity of animal and human body.
Two, the macrophages in vitro proliferative capacity experiment of mtt assay measurement biologically active polypeptide ATAVPIIFF
1) experiment reagent and instrument
Reagent: experimental animal balb/c mouse (male 6-8 week old) Shanghai Communications University's agricultural and biological institute animal are real
Test center；The biologically active polypeptide ATAVPIIFF that embodiment 1 obtains；3- (4,5- dimethylthiazole -2) -2,5- diphenyl, four nitrogen
Azoles bromide (MTT) Amresco company；LPS (lipopolysaccharides) Sigma company；Bovine serum albumin(BSA) (Bovine Serum
Albumin, BSA) Genebase company；Three lysates, the water containing 10%SDS, 5% isobutanol and 0.012mol/L HCl
Solution.
Instrument and equipment: LRH-250F biochemical cultivation case Shanghai perseverance Science and Technology Ltd.；On GL-22M high speed freezing centrifuge
Hai Luxiang instrument centrifuge Instrument Ltd.；Hera cell 150 CO2Incubator Heraeus company；Dragon Wellscan
MK3 microplate reader Labsystems company.
2) test method:
Balb/c mouse peritoneal injects 2% (w/w) the sterilizing starch solution of 2ml, and continuous injection three days, last time is injected
The neck that breaks after 24 hours is put to death.Skin of abdomen is peelled off, draws 4 DEG C of phosphate buffer (PBS) repeated flushing abdominal cavities with syringe, from
After heart pipe collects flushing liquor, supernatant is abandoned in centrifugation (1000rpm, 4 DEG C) after ten minutes, (is contained with 4 DEG C of RPMI1640 complete culture solutions
It 10%FBS) washes twice, cell viability examination is done in the dyeing of 0.2% trypan blue solution, confirms collected vibrant macrophage
Account for 95% or more.After cell counting board reading, adjustment cell concentration to suitable concentration.
It will blow and beat to the cell suspension to suspend completely and 96 porocyte culture plates, 37 DEG C, 5%CO be added with suitable volumes2
After being cultivated 4 hours under environment, inhales and abandon liquid in hole, carefully clean cell culture plate well with 37 DEG C of RPMI1640 complete culture solutions
Bottom washes away not adherent cell and cell fragment, obtains adherent peritoneal macrophage after purification.0.2ml is added in every hole
RPMI1640 complete medium, experiment small peptide sample and LPS are added after being dissolved in culture medium in advance, start cell culture.
After obtaining adherent peritoneal macrophage after purification, the every hole of experimental group adds dissolved with biologically active polypeptide
200 hole μ l/ of RPMI1640 complete culture solution (10%FBS) of ATAVPIIFF (1mg/ml), continuously cultivates 48h；Negative control group
Every hole adds 200 hole μ l/ of RPMI1640 complete culture solution (10%FBS) dissolved with BSA (500 μ g/mL)；Blank group addition
200 hole μ l/ of RPMI1640 complete culture solution (10%FBS), continuously cultivates 48h.Also, experimental group, negative control group and blank
Group sets normal group and inflammation group respectively again；LPS to final concentration of 100ng/ml is added when culture is arrived for 24 hours for inflammation group；Normal group
LPS is not added；And normally 20 hole μ l/ 5%MTT is added in 44h for group and inflammation group；100 μ are added after reaching 48h in cell culture
Three lysates in the hole l/ after dissolution overnight, survey the absorbance value in each hole to terminate culture at wavelength 570nm with microplate reader
(OD570), the calculation formula of growth index (Growth Indices) is as follows:
Wherein, blank culture solution is the RPMI1640 complete culture solution containing 10%FBS.
3) experimental result and analysis
The influence that 2 biologically active polypeptide ATAVPIIFF of table is proliferated macrophages in vitro
| Experimental group | Normal group GI | Inflammation group GI |
| Negative control group | 1 | 1 |
| ATAVPIIFF(1mg/ml) | 1.0794±0.0732** | 1.117±0.0537** |
Note: * is indicated compared with negative control, there is significant difference (P < 0.05)；* indicate compared with negative control group,
There is significant difference (P < 0.01)
Experimental result is shown in Table 2, as shown in Table 2, under conditions of adding 1mg/ml biologically active polypeptide ATAVPIIFF, just
Often the macrophage of group and inflammation group has proliferation.And compared with negative control group, there is significant difference (P < 0.01).
Illustrate that biologically active polypeptide ATAVPIIFF has significant proliferation function to macrophages in vitro.
The activity of fighting against senium of 3 biologically active peptide of embodiment is tested
One, experiment of the biologically active polypeptide ATAVPIIFF 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 ATAVPIIFF 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
ATAVPIIFF；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 ATAVPIIFF of 3mg/ only；Group 3 is blank group, mouse normal growth；Group 4 is animal
D-gal, and the physiology that stomach-filling concentration is 0.9% is subcutaneously injected daily with the dosage the nape of the neck of 500mg/kg in model group, mouse
Salt 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. 4, 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 ATAVPIIFF is to animal because the spleen aging caused by the stimulation by the bad factor has certain guarantor with atrophy
Shield effect.
Two, the experiment that biologically active polypeptide ATAVPIIFF 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 ATAVPIIFF 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；T-AOC antioxidative activities kit, Biotechnology Co., Ltd is built up in Nanjing.
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
ATAVPIIFF；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 ATAVPIIFF of 3mg/ only；Group 3 is blank group, mouse normal growth；Group 4 is animal
D-gal, and the physiology that stomach-filling concentration is 0.9% is subcutaneously injected daily with the dosage the nape of the neck of 500mg/kg in model group, mouse
Salt 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 3 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 3, 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 A TAVPIIFF to the intracorporal oxidative damage of mouse have certain protective role.
The situation of change of MDA content in 4 each group experimental animal mouse Different Organs of table
As can be known from Table 4, the liver MDA content of animal model group mouse is 26.86 ± 7.04nmol/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, illustrate the intake of polypeptide A TAVPIIFF can be effectively protected vital tissue organ from it is bad because
Son stimulation generates a large amount of lipid peroxide.
The situation of change of T-AOC in 5 each group experimental animal Mice Body of table
As known from Table 5, the liver T-AOC value of animal model group mouse is 0.68 ± 0.21U/mgprot, is compared to mould
Significant difference (P < 0.05) is presented therewith in type group, polypeptide high dose and low dosage stomach-filling group mouse；The kidney of naive mice
Dirty T-AOC content is 0.61 ± 0.25U/mgprot, and compared with animal model group mouse, low dosage stomach-filling group presents aobvious therewith
It writes sex differernce (P < 0.05), also significant difference (P < 0.01) is presented therewith in high dose stomach-filling group mouse.This result shows that, whole
In a experimental period, due to experiment animal sustained constantly by cause senescence-factor stimulation, the liver of animal model group mouse,
Renal tissue is destroyed, and the reduction of its total antioxidant capacity is caused.Compared with animal model group and blank group, polypeptide stomach-filling group is small
The total antioxidant capacity of mouse major organs maintains a higher level in by the stimulating course for causing senescence-factor always,
Illustrate that taking in biologically active polypeptide ATAVPIIFF makes animal body and its major organs self-protection function with higher.
Three, the experiment that immune cell factor in serum is acted on of biologically active polypeptide ATAVPIIFF
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 ATAVPIIFF that embodiment 1 obtains；BCA protein reagent box, Science and Technology Ltd. of Nanjing Keygen Biotech；
ELISA cell factor Quick kit (TNF-α, IL-2, IL-6 and IL-10), 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
ATAVPIIFF；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 ATAVPIIFF of 3mg/ only；Group 3 is blank group, mouse normal growth；Group 4 is animal
D-gal, and the physiology that stomach-filling concentration is 0.9% is subcutaneously injected daily with the dosage the nape of the neck of 500mg/kg in model group, mouse
Salt 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 6 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 6, Fig. 5, Fig. 6
168.01 ± 26.38pg/mL, 4.34 ± 0.76pg/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.
From Fig. 7's, as a result, it has been found that, IL-2 is as a kind of significant cell factor model in this experiment for judging aging
Do not occur conspicuousness effect in group and stomach-filling group, thus it is speculated that, it may be possible to as the model and naturally-aged employed in this experiment
Still difference or modeling period falls short of, therefore this index is caused not change.Meanwhile from Fig. 8's as a result, it has been found that, this
Biologically active polypeptide ATAVPIIFF fails to have an impact the secretion of mouse IL-10 in the period in experiment, in various mice serums
In the detection of IL-10 content, -10 content of serum IL of only normal growth group mouse is maintained at relatively low level, remaining
Each group mice serum IL-10 content, which is presented, to be increased, it may be possible to secretion access of the biologically active polypeptide ATAVPIIFF to IL-10
Without influence.
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 ATAVPIIFF 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
Ala Thr Ala Val Pro Ile Ile Phe Phe
1 5
<210> 2
<211> 27
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 2
ctactgctgt tcctattata ttttttg 27
<210> 3
<211> 319
<212> PRT
<213>artificial sequence (Artificial Sequence)
<400> 3
Leu Leu Asp Gln Phe Lys Ile Ser His Asp Pro Asn Pro Glu Val Arg
1 5 10 15
Ala Thr Ala Val Pro Ile Ile Phe Phe Glu Thr Arg Lys Gln Gly Glu
20 25 30
Arg Ile Phe His Gly Tyr Gly Val Ile Lys Asn Val Lys Leu Val Thr
35 40 45
Gln Tyr Thr Gly Ser Gly Ala Asp Lys Ala Tyr Phe Ser Asn Tyr Leu
50 55 60
Phe Thr Phe Cys Val Phe Ser Met Lys Lys Glu Gln Glu Gly Phe Asp
65 70 75 80
Trp Ser Trp Ile Glu Ala Arg Lys Gln Ala Ala Lys Asp Lys Asn Phe
85 90 95
Leu Ser Leu Ala Asn Ala Leu Ala Pro Lys Glu Trp Lys Phe Trp Ile
100 105 110
Arg Thr Gly Asp Leu Glu Lys Val Arg Arg Lys Val Tyr Gly Arg Ser
115 120 125
Thr Ser Lys Lys Glu Glu Gln Leu Pro Thr Pro Gly Ser Ala Asp Asp
130 135 140
Lys Ile Leu Asn Gln Ile Tyr Glu Tyr Tyr Arg Lys Lys Asp Asn Ser
145 150 155 160
Lys Ala His Ser Gly Asp Phe Glu Phe Glu Gly Leu Ala Lys Glu Ile
165 170 175
Thr Arg Leu Ile Ile Gly Asp Ala Cys His Asp Gly Trp Val Thr Lys
180 185 190
Ser Ser Gly Asp Gly Gly Tyr Asp Phe Val Leu Arg Val Asp Ile Gly
195 200 205
Thr Lys Gly Ile Ser Gln Val Arg Gln Val Val Leu Gly Gln Ala Lys
210 215 220
Cys Tyr Arg Arg Asp Gln Arg Ile Thr Gly Glu Ala Val Asp Arg Val
225 230 235 240
Val Ala Arg Leu Lys Arg Gly Trp Ile Ala Ala Phe Val Thr Thr Ser
245 250 255
Phe Phe Ser Asp Pro Ala Gln Arg Glu Ile Leu Glu Asp Asp Tyr Pro
260 265 270
Ile Met Leu Ile Ser Gly Lys Gln Val Ala Gln Thr Val Arg Lys Tyr
275 280 285
Ile Tyr Glu Lys Asn Ile Thr Leu Arg Glu Tyr Leu Asp Ser Leu Ser
290 295 300
Arg Asp Gln Ser Phe Lys Ser Pro Glu Asp Ile Leu Lys Glu Glu
305 310 315
Claims (10)
1. a kind of biologically active polypeptide ATAVPIIFF, which is characterized in that its amino acid sequence is Ala-Thr-Ala-Val-Pro-
Ile-Ile-Phe-Phe。
2. a kind of biologically active polypeptide ATAVPIIFF according to claim 1, which is characterized in that the bioactivity is more
Peptide derives from Lactobacillus helveticus mycoprotein.
3. encoding the nucleotide fragments of biologically active polypeptide ATAVPIIFF described in claim 1, which is characterized in that the nucleosides
The sequence of acid fragment is as shown in SEQ ID NO:2.
4. the preparation method of biologically active polypeptide ATAVPIIFF as described in claim 1, which is characterized in that pass through genetic engineering
Method it is artificial synthesized or Lactobacillus helveticus thallus is directly obtained by the method that clasmatosis isolates and purifies, or directly pass through
Chemical synthesis preparation.
5. the application of biologically active polypeptide ATAVPIIFF as described in claim 1, which is characterized in that the biologically active polypeptide
Application of the ATAVPIIFF in food, health care product, drug or the cosmetics that preparation has immunoloregulation function.
6. the application of biologically active polypeptide ATAVPIIFF as described in claim 1, which is characterized in that the biologically active polypeptide
Application of the ATAVPIIFF in the food, health care product or drug that preparation has anti-senescence function.
7. the application of biologically active polypeptide ATAVPIIFF as described in claim 1, which is characterized in that the biologically active polypeptide
Application of the ATAVPIIFF in the food, health care product or drug that preparation has immunoloregulation function and anti-senescence function.
8. a kind of immunological regulation product, which is characterized in that including biologically active polypeptide ATAVPIIFF as described in claim 1 or
The derivative of the biologically active polypeptide ATAVPIIFF；The immunological regulation product includes immunological regulation food, immunological regulation
Health care product, immunoregulation medicament or immunological regulation cosmetics；The derivative of the biologically active polypeptide ATAVPIIFF, refers to
On the amino acid side groups of biologically active polypeptide ATAVPIIFF, aminoterminal or c-terminus carry out hydroxylating, carboxylated, carbonyl
Change, methylation, acetylation, phosphorylation, esterification or glycosylation modified, obtained polypeptide derivative.
9. a kind of anti-aging product, which is characterized in that including biologically active polypeptide ATAVPIIFF as described in claim 1 or institute
State the derivative of biologically active polypeptide ATAVPIIFF；The anti-aging product include antisenility cistanche food, antisenescence health product or
Antiaging agent；The derivative of the biologically active polypeptide ATAVPIIFF, refers to the ammonia in biologically active polypeptide ATAVPIIFF
On base acid side-chain radical, aminoterminal or c-terminus carry out hydroxylating, carboxylated, carbonylation, methylation, acetylation, phosphorylation, ester
Change or glycosylation modified, obtained polypeptide derivative.
10. a kind of product with immunoloregulation function and anti-senescence function, which is characterized in that including as described in claim 1
The derivative of biologically active polypeptide ATAVPIIFF or the biologically active polypeptide ATAVPIIFF；With immunoloregulation function and resist
The product of aging function includes food, health care product or drug；The derivative of the biologically active polypeptide ATAVPIIFF, refers to
On the amino acid side groups of biologically active polypeptide ATAVPIIFF, aminoterminal or c-terminus carry out hydroxylating, carboxylated, carbonyl
Change, methylation, acetylation, phosphorylation, esterification or glycosylation modified, obtained polypeptide derivative.
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| CN112661829A (en) * | 2021-01-19 | 2021-04-16 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide GGYGSGGGSGGYGSRRF, and preparation method and application thereof |
| CN112679597A (en) * | 2021-01-19 | 2021-04-20 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide SEPKPIFF and preparation method and application thereof |
| CN112679598A (en) * | 2021-01-19 | 2021-04-20 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide SGVSLAALKKALAAAGYDVEK, and preparation method and application thereof |
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| CN112745379A (en) * | 2021-01-22 | 2021-05-04 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide with amino acid structure RDNKKTRIIPR, and preparation method and application thereof |
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| CN112745382A (en) * | 2021-01-22 | 2021-05-04 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide with amino acid structure LTVINQTQKENLR, and preparation method and application thereof |
| CN112759635A (en) * | 2021-01-21 | 2021-05-07 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide with amino acid structure VAKVTGGAASKL, and preparation method and application thereof |
| CN112812169A (en) * | 2021-01-21 | 2021-05-18 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide with amino acid structure APKIQRLVTPR, and preparation method and application thereof |
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| CN112679597A (en) * | 2021-01-19 | 2021-04-20 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide SEPKPIFF and preparation method and application thereof |
| CN112679598A (en) * | 2021-01-19 | 2021-04-20 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide SGVSLAALKKALAAAGYDVEK, and preparation method and application thereof |
| CN112759635A (en) * | 2021-01-21 | 2021-05-07 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide with amino acid structure VAKVTGGAASKL, and preparation method and application thereof |
| CN112812169A (en) * | 2021-01-21 | 2021-05-18 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide with amino acid structure APKIQRLVTPR, and preparation method and application thereof |
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| CN112745382A (en) * | 2021-01-22 | 2021-05-04 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide with amino acid structure LTVINQTQKENLR, and preparation method and application thereof |
| CN112745380B (en) * | 2021-01-22 | 2022-04-08 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide with amino acid structure RAGLQFPVGRVH, and preparation method and application thereof |
| CN112745381B (en) * | 2021-01-22 | 2022-05-31 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide with amino acid structure NIRNIGKTLVTR, and preparation method and application thereof |
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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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