CN107759681A - A kind of biologically active polypeptide INNQFLPYPYYAKPA and its preparation method and application - Google Patents
A kind of biologically active polypeptide INNQFLPYPYYAKPA and its preparation method and application Download PDFInfo
- Publication number
- CN107759681A CN107759681A CN201711250938.9A CN201711250938A CN107759681A CN 107759681 A CN107759681 A CN 107759681A CN 201711250938 A CN201711250938 A CN 201711250938A CN 107759681 A CN107759681 A CN 107759681A
- Authority
- CN
- China
- Prior art keywords
- innqflpypyyakpa
- biologically active
- active polypeptide
- polypeptide
- derivative
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 129
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 104
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 97
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 230000036541 health Effects 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 16
- 235000013305 food Nutrition 0.000 claims abstract description 16
- 150000001413 amino acids Chemical group 0.000 claims abstract description 14
- 230000002519 immonomodulatory effect Effects 0.000 claims abstract description 11
- 230000003005 anti-senility effect Effects 0.000 claims abstract description 3
- 230000006870 function Effects 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 19
- 239000000047 product Substances 0.000 claims description 17
- 230000033228 biological regulation Effects 0.000 claims description 14
- 230000001900 immune effect Effects 0.000 claims description 13
- 235000013336 milk Nutrition 0.000 claims description 13
- 239000008267 milk Substances 0.000 claims description 13
- 210000004080 milk Anatomy 0.000 claims description 13
- 230000003712 anti-aging effect Effects 0.000 claims description 11
- 239000012634 fragment Substances 0.000 claims description 8
- 230000021736 acetylation Effects 0.000 claims description 6
- 238000006640 acetylation reaction Methods 0.000 claims description 6
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 6
- 230000032050 esterification Effects 0.000 claims description 6
- 238000005886 esterification reaction Methods 0.000 claims description 6
- 230000013595 glycosylation Effects 0.000 claims description 6
- 238000006206 glycosylation reaction Methods 0.000 claims description 6
- 230000000640 hydroxylating effect Effects 0.000 claims description 6
- 230000026731 phosphorylation Effects 0.000 claims description 6
- 238000006366 phosphorylation reaction Methods 0.000 claims description 6
- 239000002537 cosmetic Substances 0.000 claims description 5
- 239000002773 nucleotide Substances 0.000 claims description 5
- 125000003729 nucleotide group Chemical group 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 235000013365 dairy product Nutrition 0.000 claims description 4
- 241000005787 Cistanche Species 0.000 claims description 2
- 230000007365 immunoregulation Effects 0.000 claims description 2
- 230000009711 regulatory function Effects 0.000 claims description 2
- 238000002474 experimental method Methods 0.000 abstract description 28
- 210000002540 macrophage Anatomy 0.000 abstract description 13
- 230000000694 effects Effects 0.000 abstract description 10
- 230000032683 aging Effects 0.000 abstract description 8
- 238000004458 analytical method Methods 0.000 abstract description 8
- 102000004190 Enzymes Human genes 0.000 abstract description 6
- 108090000790 Enzymes Proteins 0.000 abstract description 6
- 201000010099 disease Diseases 0.000 abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
- 238000000338 in vitro Methods 0.000 abstract description 6
- BOJYMMBYBNOOGG-DCAQKATOSA-N Lys-Pro-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O BOJYMMBYBNOOGG-DCAQKATOSA-N 0.000 abstract description 3
- MWUYSCVVPVITMW-IGNZVWTISA-N Tyr-Tyr-Ala Chemical compound C([C@@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 MWUYSCVVPVITMW-IGNZVWTISA-N 0.000 abstract description 3
- 208000015181 infectious disease Diseases 0.000 abstract description 3
- 210000004698 lymphocyte Anatomy 0.000 abstract description 3
- 230000001717 pathogenic effect Effects 0.000 abstract description 3
- XZUUUKNKNWVPHQ-JYJNAYRXSA-N Gln-Phe-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O XZUUUKNKNWVPHQ-JYJNAYRXSA-N 0.000 abstract description 2
- QYZYJFXHXYUZMZ-UGYAYLCHSA-N Ile-Asn-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N QYZYJFXHXYUZMZ-UGYAYLCHSA-N 0.000 abstract description 2
- IALSFJSONJZBKB-HRCADAONSA-N Pro-Tyr-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N3CCC[C@@H]3C(=O)O IALSFJSONJZBKB-HRCADAONSA-N 0.000 abstract description 2
- 230000003035 anti-peroxidant effect Effects 0.000 abstract description 2
- 108010057821 leucylproline Proteins 0.000 abstract description 2
- 230000036259 sexual stimuli Effects 0.000 abstract description 2
- 230000003053 immunization Effects 0.000 abstract 1
- 238000002649 immunization Methods 0.000 abstract 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 52
- 239000011347 resin Substances 0.000 description 20
- 229920005989 resin Polymers 0.000 description 20
- 238000005516 engineering process Methods 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 14
- 230000009267 minimal disease activity Effects 0.000 description 14
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 239000007788 liquid Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 241000255601 Drosophila melanogaster Species 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 239000002158 endotoxin Substances 0.000 description 7
- 229920006008 lipopolysaccharide Polymers 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 108010076119 Caseins Proteins 0.000 description 6
- 102000011632 Caseins Human genes 0.000 description 6
- 206010057249 Phagocytosis Diseases 0.000 description 6
- 239000012980 RPMI-1640 medium Substances 0.000 description 6
- 239000005018 casein Substances 0.000 description 6
- 230000002708 enhancing effect Effects 0.000 description 6
- 239000001963 growth medium Substances 0.000 description 6
- 238000007689 inspection Methods 0.000 description 6
- 230000008782 phagocytosis Effects 0.000 description 6
- 150000003053 piperidines Chemical class 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- KVYRCBOUKXJXDK-UHFFFAOYSA-N 3,4-dimethylphenazine-1,2-diamine hydrochloride Chemical compound Cl.C1=CC=CC2=NC3=C(C)C(C)=C(N)C(N)=C3N=C21 KVYRCBOUKXJXDK-UHFFFAOYSA-N 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 239000008363 phosphate buffer Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 230000001850 reproductive effect Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 108010077544 Chromatin Proteins 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 230000001464 adherent effect Effects 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 230000003078 antioxidant effect Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 210000003483 chromatin Anatomy 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 230000036039 immunity Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 210000003024 peritoneal macrophage Anatomy 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 240000008042 Zea mays Species 0.000 description 3
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 3
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 235000021240 caseins Nutrition 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 235000005822 corn Nutrition 0.000 description 3
- 235000020247 cow milk Nutrition 0.000 description 3
- 238000005520 cutting process Methods 0.000 description 3
- 238000004042 decolorization Methods 0.000 description 3
- 238000001152 differential interference contrast microscopy Methods 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 240000001131 Nostoc commune Species 0.000 description 2
- 235000013817 Nostoc commune Nutrition 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- CUTSCJHLMGPBEJ-UHFFFAOYSA-N [N].CN(C)C=O Chemical compound [N].CN(C)C=O CUTSCJHLMGPBEJ-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 108010044940 alanylglutamine Proteins 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- -1 aromatic amino acid Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000005034 decoration Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 108010050848 glycylleucine Proteins 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000010183 spectrum analysis Methods 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 235000021246 κ-casein Nutrition 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- ZQOILFFBJUNGRA-NMVUUJPQSA-N (4s)-4-[[(2s)-2-amino-3-methylbutanoyl]amino]-5-[(2s)-2-[[(2s,3s)-1-[(2s)-2-[[(1s)-1-carboxy-2-(4-hydroxyphenyl)ethyl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-oxopentanoic acid Chemical compound N([C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)C(C)C ZQOILFFBJUNGRA-NMVUUJPQSA-N 0.000 description 1
- UWSONZCNXUSTKW-UHFFFAOYSA-N 4,5-Dimethylthiazole Chemical compound CC=1N=CSC=1C UWSONZCNXUSTKW-UHFFFAOYSA-N 0.000 description 1
- KVWLTGNCJYDJET-LSJOCFKGSA-N Ala-Arg-His Chemical compound C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N KVWLTGNCJYDJET-LSJOCFKGSA-N 0.000 description 1
- NINQYGGNRIBFSC-CIUDSAMLSA-N Ala-Lys-Ser Chemical compound NCCCC[C@H](NC(=O)[C@@H](N)C)C(=O)N[C@@H](CO)C(O)=O NINQYGGNRIBFSC-CIUDSAMLSA-N 0.000 description 1
- IYKVSFNGSWTTNZ-GUBZILKMSA-N Ala-Val-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N IYKVSFNGSWTTNZ-GUBZILKMSA-N 0.000 description 1
- 241000024188 Andala Species 0.000 description 1
- QCTOLCVIGRLMQS-HRCADAONSA-N Arg-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O QCTOLCVIGRLMQS-HRCADAONSA-N 0.000 description 1
- QPTAGIPWARILES-AVGNSLFASA-N Asn-Gln-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QPTAGIPWARILES-AVGNSLFASA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- BVFQOPGFOQVZTE-ACZMJKKPSA-N Cys-Gln-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O BVFQOPGFOQVZTE-ACZMJKKPSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108700002304 Drosophila can Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- MADFVRSKEIEZHZ-DCAQKATOSA-N Gln-Gln-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N MADFVRSKEIEZHZ-DCAQKATOSA-N 0.000 description 1
- ZQPOVSJFBBETHQ-CIUDSAMLSA-N Gln-Glu-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZQPOVSJFBBETHQ-CIUDSAMLSA-N 0.000 description 1
- FTIJVMLAGRAYMJ-MNXVOIDGSA-N Gln-Ile-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCC(N)=O FTIJVMLAGRAYMJ-MNXVOIDGSA-N 0.000 description 1
- LTUVYLVIZHJCOQ-KKUMJFAQSA-N Glu-Arg-Phe Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O LTUVYLVIZHJCOQ-KKUMJFAQSA-N 0.000 description 1
- ALCAUWPAMLVUDB-FXQIFTODSA-N Glu-Gln-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O ALCAUWPAMLVUDB-FXQIFTODSA-N 0.000 description 1
- GXMXPCXXKVWOSM-KQXIARHKSA-N Glu-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)O)N GXMXPCXXKVWOSM-KQXIARHKSA-N 0.000 description 1
- CUPSDFQZTVVTSK-GUBZILKMSA-N Glu-Lys-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCC(O)=O CUPSDFQZTVVTSK-GUBZILKMSA-N 0.000 description 1
- JWNZHMSRZXXGTM-XKBZYTNZSA-N Glu-Ser-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JWNZHMSRZXXGTM-XKBZYTNZSA-N 0.000 description 1
- GZUKEVBTYNNUQF-WDSKDSINSA-N Gly-Ala-Gln Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(O)=O GZUKEVBTYNNUQF-WDSKDSINSA-N 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241000892865 Heros Species 0.000 description 1
- 241000167880 Hirundinidae Species 0.000 description 1
- LVXFNTIIGOQBMD-SRVKXCTJSA-N His-Leu-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O LVXFNTIIGOQBMD-SRVKXCTJSA-N 0.000 description 1
- NCSIQAFSIPHVAN-IUKAMOBKSA-N Ile-Asn-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N NCSIQAFSIPHVAN-IUKAMOBKSA-N 0.000 description 1
- HTDRTKMNJRRYOJ-SIUGBPQLSA-N Ile-Gln-Tyr Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HTDRTKMNJRRYOJ-SIUGBPQLSA-N 0.000 description 1
- KLBVGHCGHUNHEA-BJDJZHNGSA-N Ile-Leu-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)O)N KLBVGHCGHUNHEA-BJDJZHNGSA-N 0.000 description 1
- 108010055461 Ile-Pro-Pro-Lys-Lys-Asn-Gln-Asp-Lys-Thr-Glu Proteins 0.000 description 1
- 108010065920 Insulin Lispro Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- WXHFZJFZWNCDNB-KKUMJFAQSA-N Leu-Asn-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 WXHFZJFZWNCDNB-KKUMJFAQSA-N 0.000 description 1
- HFBCHNRFRYLZNV-GUBZILKMSA-N Leu-Glu-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O HFBCHNRFRYLZNV-GUBZILKMSA-N 0.000 description 1
- USLNHQZCDQJBOV-ZPFDUUQYSA-N Leu-Ile-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(O)=O USLNHQZCDQJBOV-ZPFDUUQYSA-N 0.000 description 1
- UCXQIIIFOOGYEM-ULQDDVLXSA-N Leu-Pro-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 UCXQIIIFOOGYEM-ULQDDVLXSA-N 0.000 description 1
- KZZCOWMDDXDKSS-CIUDSAMLSA-N Leu-Ser-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O KZZCOWMDDXDKSS-CIUDSAMLSA-N 0.000 description 1
- QWWPYKKLXWOITQ-VOAKCMCISA-N Leu-Thr-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(C)C QWWPYKKLXWOITQ-VOAKCMCISA-N 0.000 description 1
- BQVUABVGYYSDCJ-ZFWWWQNUSA-N Leu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](N)CC(C)C)C(O)=O)=CNC2=C1 BQVUABVGYYSDCJ-ZFWWWQNUSA-N 0.000 description 1
- SLQJJFAVWSZLBL-BJDJZHNGSA-N Lys-Ile-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCCCN SLQJJFAVWSZLBL-BJDJZHNGSA-N 0.000 description 1
- IMDJSVBFQKDDEQ-MGHWNKPDSA-N Lys-Tyr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CCCCN)N IMDJSVBFQKDDEQ-MGHWNKPDSA-N 0.000 description 1
- CRVSHEPROQHVQT-AVGNSLFASA-N Met-Met-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)O)N CRVSHEPROQHVQT-AVGNSLFASA-N 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 1
- BQVUABVGYYSDCJ-UHFFFAOYSA-N Nalpha-L-Leucyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)CC(C)C)C(O)=O)=CNC2=C1 BQVUABVGYYSDCJ-UHFFFAOYSA-N 0.000 description 1
- 102000001490 Opioid Peptides Human genes 0.000 description 1
- 108010093625 Opioid Peptides Proteins 0.000 description 1
- 208000025174 PANDAS Diseases 0.000 description 1
- 208000021155 Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection Diseases 0.000 description 1
- 240000000220 Panda oleosa Species 0.000 description 1
- 235000016496 Panda oleosa Nutrition 0.000 description 1
- SZYBZVANEAOIPE-UBHSHLNASA-N Phe-Met-Ala Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O SZYBZVANEAOIPE-UBHSHLNASA-N 0.000 description 1
- XDMMOISUAHXXFD-SRVKXCTJSA-N Phe-Ser-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O XDMMOISUAHXXFD-SRVKXCTJSA-N 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- YTWNSIDWAFSEEI-RWMBFGLXSA-N Pro-His-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CN=CN2)C(=O)N3CCC[C@@H]3C(=O)O YTWNSIDWAFSEEI-RWMBFGLXSA-N 0.000 description 1
- SOACYAXADBWDDT-CYDGBPFRSA-N Pro-Ile-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O SOACYAXADBWDDT-CYDGBPFRSA-N 0.000 description 1
- WHNJMTHJGCEKGA-ULQDDVLXSA-N Pro-Phe-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O WHNJMTHJGCEKGA-ULQDDVLXSA-N 0.000 description 1
- RFWXYTJSVDUBBZ-DCAQKATOSA-N Pro-Pro-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 RFWXYTJSVDUBBZ-DCAQKATOSA-N 0.000 description 1
- RMJZWERKFFNNNS-XGEHTFHBSA-N Pro-Thr-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O RMJZWERKFFNNNS-XGEHTFHBSA-N 0.000 description 1
- GZNYIXWOIUFLGO-ZJDVBMNYSA-N Pro-Thr-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZNYIXWOIUFLGO-ZJDVBMNYSA-N 0.000 description 1
- XDKKMRPRRCOELJ-GUBZILKMSA-N Pro-Val-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 XDKKMRPRRCOELJ-GUBZILKMSA-N 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- MIJWOJAXARLEHA-WDSKDSINSA-N Ser-Gly-Glu Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O MIJWOJAXARLEHA-WDSKDSINSA-N 0.000 description 1
- RRVFEDGUXSYWOW-BZSNNMDCSA-N Ser-Phe-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O RRVFEDGUXSYWOW-BZSNNMDCSA-N 0.000 description 1
- ADJDNJCSPNFFPI-FXQIFTODSA-N Ser-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO ADJDNJCSPNFFPI-FXQIFTODSA-N 0.000 description 1
- BSXKBOUZDAZXHE-CIUDSAMLSA-N Ser-Pro-Glu Chemical compound [H]N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O BSXKBOUZDAZXHE-CIUDSAMLSA-N 0.000 description 1
- FHXGMDRKJHKLKW-QWRGUYRKSA-N Ser-Tyr-Gly Chemical compound OC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=C(O)C=C1 FHXGMDRKJHKLKW-QWRGUYRKSA-N 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- VGYBYGQXZJDZJU-XQXXSGGOSA-N Thr-Glu-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O VGYBYGQXZJDZJU-XQXXSGGOSA-N 0.000 description 1
- XOWKUMFHEZLKLT-CIQUZCHMSA-N Thr-Ile-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O XOWKUMFHEZLKLT-CIQUZCHMSA-N 0.000 description 1
- PAXANSWUSVPFNK-IUKAMOBKSA-N Thr-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H]([C@@H](C)O)N PAXANSWUSVPFNK-IUKAMOBKSA-N 0.000 description 1
- GVMXJJAJLIEASL-ZJDVBMNYSA-N Thr-Pro-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O GVMXJJAJLIEASL-ZJDVBMNYSA-N 0.000 description 1
- RVMNUBQWPVOUKH-HEIBUPTGSA-N Thr-Ser-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O RVMNUBQWPVOUKH-HEIBUPTGSA-N 0.000 description 1
- QNXZCKMXHPULME-ZNSHCXBVSA-N Thr-Val-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N)O QNXZCKMXHPULME-ZNSHCXBVSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- JLTQXEOXIJMCLZ-ZVZYQTTQSA-N Trp-Gln-Val Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O)=CNC2=C1 JLTQXEOXIJMCLZ-ZVZYQTTQSA-N 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- SLLKXDSRVAOREO-KZVJFYERSA-N Val-Ala-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)N)O SLLKXDSRVAOREO-KZVJFYERSA-N 0.000 description 1
- UZDHNIJRRTUKKC-DLOVCJGASA-N Val-Gln-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](C(C)C)C(=O)O)N UZDHNIJRRTUKKC-DLOVCJGASA-N 0.000 description 1
- VXDSPJJQUQDCKH-UKJIMTQDSA-N Val-Ile-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N VXDSPJJQUQDCKH-UKJIMTQDSA-N 0.000 description 1
- BTWMICVCQLKKNR-DCAQKATOSA-N Val-Leu-Ser Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C([O-])=O BTWMICVCQLKKNR-DCAQKATOSA-N 0.000 description 1
- JVGDAEKKZKKZFO-RCWTZXSCSA-N Val-Val-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N)O JVGDAEKKZKKZFO-RCWTZXSCSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 1
- 230000002605 anti-dotal effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 108010092854 aspartyllysine Proteins 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229940021722 caseins Drugs 0.000 description 1
- 239000012930 cell culture fluid Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 210000003022 colostrum Anatomy 0.000 description 1
- 235000021277 colostrum Nutrition 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 108010085325 histidylproline 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
- 229940088592 immunologic factor Drugs 0.000 description 1
- 230000006872 improvement 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
- 210000000936 intestine Anatomy 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical group Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 1
- 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
- 230000004792 oxidative damage Effects 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 108010073025 phenylalanylphenylalanine Proteins 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000197 pyrolysis Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 230000037380 skin damage Effects 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 108010020532 tyrosyl-proline Proteins 0.000 description 1
- 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
- 239000003643 water by type Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 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
- C07K14/435—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, more particularly to a kind of biologically active polypeptide INNQFLPYPYYAKPA and its preparation method and application, its amino acid sequence of biologically active polypeptide INNQFLPYPYYAKPA is Ile Asn Asn Gln Phe Leu Pro Tyr Pro Tyr Tyr Ala Lys Pro Ala.By the experiment of ion vitro immunization function point analysis, internal Antisenility Experiment, demonstrating polypeptide INNQFLPYPYYAKPA has preferable immunoloregulation function and activity of fighting against senium, on the one hand, the biologically active polypeptide INNQFLPYPYYAKPA of the present invention can strengthen the in-vitro multiplication ability of lymphocyte and macrophage, the ability that body resists extraneous pathogenic infection is improved, reduces the body incidence of disease；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 immunoloregulation 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 INNQFLPYPYYAKPA and its preparation
Methods and applications.
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.
Immune-active peptides are to obtain and prove that one kind biology of its physiologically active is living from breast first after opioid peptides discovery
Property polypeptide.Jolles in 1981 et al. has found first, using trypsin hydrolysis people lactoprotein, can obtain an amino acid sequence
Val-Glu-Pro-Ile-Pro-Tyr hexapeptide is classified as, experiment in vitro proves that the peptide can strengthen 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 phagocytosis and enhancing of the sheep erythrocyte to mouse peritoneal macrophages for kerekou pneumonia primary
The resistance of bacterium.Li Su duckweeds et al. find rat peritoneal macrophages with newborn source immunomodulatory peptides (PGPIPN) the feeding rat of synthesis
The phagocytosis immunoloregulation function related to red blood cell have significant enhancing.
Research shows that immune-active peptides can not only strengthen immunity of organisms, stimulates the propagation of body lymphocyte, enhancing
The phagocytic function of macrophage, promote the release of cell factor, improve the ability that body resists extraneous pathogenic infection, reduce machine
The body incidence of disease, and the immunological rejection of body will not be caused.
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 INNQFLPYPYYAKPA and preparation method thereof and answer
With.
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 INNQFLPYPYYAKPA, its amino acid sequence are Ile-
Asn-Asn-Gln-Phe-Leu-Pro-Tyr-Pro-Tyr-Tyr-Ala-Lys-Pro-Ala, such as SEQ ID NO：Shown in 1.
Preferably, the biologically active polypeptide is milk-derived.κ-casein is derive specifically from, and is κ-ss-casein variants
The amino acid residue that A is the 72nd~86.κ-ss-casein variants A amino acid sequences such as SEQ ID NO：Shown in 3.
The amino acid sequence of κ-casein and corresponding nucleotides sequence are classified as existing technology, encode κ-ss-casein variants A
The biologically active polypeptide INNQFLPYPYYAKPA of the nucleotide fragments energy encoding mature of 72nd~86 amino acids residue.
Preferably, the biologically active polypeptide has immunoloregulation function and anti-senescence function.
Second aspect of the present invention, there is provided the nucleotide fragments of the biologically active polypeptide INNQFLPYPYYAKPA are encoded,
Its sequence is：5 '-att aat aat caa ttt ctg cca tac cca tat tat gca aag cca gct-3 ', such as
SEQ ID NO：Shown in 2.
Third aspect present invention, there is provided the preparation method of the biologically active polypeptide INNQFLPYPYYAKPA, Ke Yitong
The method for crossing genetic engineering is artificial synthesized, can be directly obtained, can directly led to by the method isolated and purified from dairy products
Cross chemical synthesis preparation.
Fourth aspect present invention, there is provided the biologically active polypeptide INNQFLPYPYYAKPA is being prepared with immune tune
Save the application in food, health products, medicine or the cosmetics of function.
Fifth aspect present invention, there is provided the biologically active polypeptide INNQFLPYPYYAKPA has anti-aging in preparation
Application in the food of function, health products or medicine.
Sixth aspect present invention, there is provided the biologically active polypeptide INNQFLPYPYYAKPA has simultaneously in preparation to exempt from
Application in the food of epidemic disease regulatory function and anti-senescence function, health products or medicine.
Specifically, biologically active polypeptide INNQFLPYPYYAKPA of the invention, which can be used for preparing, reduces free radical pair
The cosmetics of skin damage, prepare the medicine with immunological regulation and/or anti-aging；And because the bioactivity of the present invention is more
Product after peptide INNQFLPYPYYAKPA is degraded by intestines and stomach still has bioactivity, therefore can be also used for preparing acid
The food such as milk, the health products for adjusting immunity, and the oral medicine being used to prepare with immunological regulation and/or anti-aging.
Seventh aspect present invention, there is provided a kind of immunological regulation product, including the biologically active polypeptide
INNQFLPYPYYAKPA or described biologically active polypeptides INNQFLPYPYYAKPA derivative；Described immunological regulation product bag
Include immunological regulation food, immunological regulation health products, immunoregulation medicament or immunological regulation cosmetics；The biologically active polypeptide
INNQFLPYPYYAKPA derivative, refer on biologically active polypeptide INNQFLPYPYYAKPA amino acid side groups,
Aminoterminal or c-terminus carry out hydroxylating, carboxylated, be carbonylated, methylate, acetylation, phosphorylation, esterification or glycosylation etc. are repaiied
Decorations, obtained polypeptide derivative.
Eighth aspect present invention, there is provided a kind of anti-aging product, including the biologically active polypeptide
INNQFLPYPYYAKPA or described biologically active polypeptides INNQFLPYPYYAKPA derivative；Described anti-aging product includes
Antisenility cistanche food, antisenescence health product or antiaging agent；The derivative of the biologically active polypeptide INNQFLPYPYYAKPA,
Refer on biologically active polypeptide INNQFLPYPYYAKPA amino acid side groups, aminoterminal or c-terminus carry out hydroxylating,
Carboxylated, be carbonylated, methylate, acetylation, phosphorylation, the modification such as esterification or glycosylation, obtained polypeptide derivative.
Ninth aspect present invention, there is provided product a kind of while that there is immunoloregulation function and anti-senescence function, including
The derivative of the biologically active polypeptide INNQFLPYPYYAKPA or described biologically active polypeptides INNQFLPYPYYAKPA；Have
The product of immunoloregulation function and anti-senescence function includes food, health products or medicine；The biologically active polypeptide
INNQFLPYPYYAKPA derivative, refer on biologically active polypeptide INNQFLPYPYYAKPA amino acid side groups,
Aminoterminal or c-terminus carry out hydroxylating, carboxylated, be carbonylated, methylate, acetylation, phosphorylation, esterification or glycosylation etc. are repaiied
Decorations, obtained polypeptide derivative.
Biologically active polypeptide INNQFLPYPYYAKPA's of the present invention has the beneficial effect that：The milk-derived bioactivity of the present invention
Polypeptide INNQFLPYPYYAKPA has preferably regulation immunity of organisms activity and activity of fighting against senium；On the one hand, life of the invention
Thing active peptides INNQFLPYPYYAKPA can strengthen the in-vitro multiplication ability of lymphocyte and macrophage, improve body and support
The ability of extraneous pathogenic infection is driven, reduces the body incidence of disease；On the other hand, it is possible to increase the work of internal anti-peroxidation enzyme system
Power, the function of enhancing body resistance external source sexual stimulus, so as to reduce organism aging process, aging and sick probability, has to exploitation
The dairy products and health products of immunoloregulation function and anti-senescence function tool are of great significance.
Brief description of the drawings
Fig. 1：Mass chromatography extraction figure (m/z=899.9621)；
Fig. 2：Mass-to-charge ratio is the second order mses figure of 899.9621 fragment；
Fig. 3：Mass-to-charge ratio is 899.9621 polypeptide az, by crack conditions；
Fig. 4：Biologically active polypeptide INNQFLPYPYYAKPA macrophages in vitro multiplication capacity experiment；
Fig. 5：Influence situations of the biologically active polypeptide INNQFLPYPYYAKPA to drosophila survival rate.
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, 1989and 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 INNQFLPYPYYAKPA'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.
After 2.2 hours, resin is washed with nitrogen-dimethylformamide (DMF) of 3 times of resin volumes, is then drained, so weight
It is multiple 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 Ile 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.
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
Washed four times, drained stand-by with the DMF of 3 times of resin volumes afterwards.
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.
After 10.1 hours, take 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. according to step 9-11 connect successively amino acid Asn, Asn, Gln, Phe, Leu, Pro, Tyr, Pro, Tyr, Tyr,
Ala, Lys, Pro and Ala.
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 INNQFLPYPYYAKPA.
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 INNQFLPYPYYAKPA carries out chromatography and mass spectral analysis, and its mass chromatography extraction figure is as shown in figure 1, extract this peak
As shown in Figures 2 and 3, the polypeptide mass-to-charge ratio that can obtain this peak is 899.9621Da for second order mses figure and az, by crack conditions, during reservation
Between be 74.1min.
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
899.9621Da fragment sequence be Ile-Asn-Asn-Gln-Phe-Leu-Pro-Tyr-Pro-Tyr-Tyr-Ala-Lys-
Pro-Ala
(INNQFLPYPYYAKPA) SEQ ID NO, are designated as：1.The fragment is residual with κ-ss-casein variants A's the 72nd~86
Basic sequence is corresponding, and the GenBank numberings of κ-casamino acid sequence are AAA30433.1, and sequence is shown in SEQ ID NO：3.
The regulation immunity of organisms activity experiment of the biologically active peptide of embodiment 2
First, mtt assay measure biologically active polypeptide INNQFLPYPYYAKPA macrophages in vitro multiplication capacity experiment
1. experiment reagent and instrument：
Reagent：Experimental animal balb/c mouse (male 6-8 week old) Shanghai Communications University is agriculture real with biological institute animal
Test center；The milk-derived biologically active polypeptide INNQFLPYPYYAKPA that embodiment 1 obtains；3- (4,5- dimethylthiazole -2) -2,
5- diphenyltetrazolium bromide bromides (MTT) Amresco companies；LPS (lipopolysaccharides) Sigma companies；Bovine serum albumin(BSA) (Bovine
Serum Albumin, BSA) Genebase companies；Three lysates, containing 10%SDS, 5% isobutanol and 0.012mol/L
The HCl aqueous solution.
Instrument and equipment：LRH-250F biochemical cultivation cases Shanghai perseverance Science and Technology Ltd.；On GL-22M high speed freezing centrifuges
Hai Luxiang instrument centrifuges Instrument Ltd.；Hera cell 150 CO2Incubator Heraeus companies；Dragon Wellscan
MK3 ELIASA Labsystems companies.
2. experimental method：
Balb/c mouse peritoneal injections 2ml 2% (w/w) sterilizing starch solutions, 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, 4 DEG C of phosphate buffers (PBS) is drawn with syringe and rinses abdominal cavity repeatedly, from
After heart pipe collects flushing liquor, centrifugation (1000rpm, 4 DEG C) abandons supernatant after 10 minutes, (is contained with 4 DEG C of RPMI1640 complete culture solutions
10%FBS) wash twice, cell viability examination is done in the dyeing of 0.2% trypan blue solution, confirms the vibrant macrophage collected
Account for more than 95%.After cell counting count board reading, adjustment cell concentration to suitable concn.
It will blow and beat to the cell suspension to suspend completely and added 96 porocyte culture plates, 37 DEG C, 5%CO with suitable volumes2
After being cultivated 4 hours under environment, liquid in hole is abandoned in suction, and cell culture plate well is carefully cleaned with 37 DEG C of RPMI1640 complete culture solutions
Bottom, not adherent cell and cell fragment are washed away, obtain adherent peritoneal macrophage after purification.0.2ml is added per hole
RPMI1640 complete mediums, experiment add after being dissolved in culture medium in advance with small peptide sample and LPS, start cell culture.
It is 2 × 10 to add number of cells5/ ml μ l/ the holes of cell suspension 100, adherent addition after purification are more containing bioactivity
The μ l/ holes of RPMI1640 complete culture solutions (10%FBS) 200 of peptide (100,500,1000 μ g/mL), continuous culture 48 hours are scorching
Disease group added LPS to final concentration 100ng/ml at 24 hours.The μ l/ holes of 5%MTT 20 are added at 44 hours, after reaching 48 hours
Three lysates in 100 μ l/ holes are added to terminate culture, after dissolving overnight, survey the suction in each hole with ELIASA under wavelength 570nm
Shading value (OD570), the calculation formula of growth index (Growth Indices) are as follows：
Wherein, for blank group not apply small peptide and BSA cell treatment group, BSA groups are negative control.
3. experimental result and analysis：
Experimental result is shown in Fig. 4, and the addition concentration of biologically active polypeptide (INNQFLPYPYYAKPA) is respectively in experimental group
1000,500,100 μ g/mL, blank group add the PBS of respective amount as blank control, represented in the case where no LPS is stimulated
The proliferative conditions of macrophage.Compared with blank control group, add the polypeptide INNQFLPYPYYAKPA experimental groups of various concentrations with
The increase of experimental concentration, the multiplication capacity of macrophage is gradually increasing, and when concentration is 1000,500 μ g/mL, is had notable
Sex differernce (P<0.05).Illustrate that biologically active polypeptide INNQFLPYPYYAKPA has the ability for promoting macrophage proliferation.
2nd, biologically active polypeptide INNQFLPYPYYAKPA rush macrophage phagocytosis dimethyl diaminophenazine chloride capacity experimental
1. experiment reagent and instrument：
Reagent：Experimental animal balb/c mouse (male 6-8 week old) Shanghai Communications University is agriculture real with biological institute animal
Test center；The milk-derived biologically active polypeptide INNQFLPYPYYAKPA that embodiment 1 obtains；LPS, purchased from Sigma companies；It is neutral
Red colouring liquid, green skies biotechnology research institute production.
Instrument and equipment：LRH-250F biochemical cultivation cases Shanghai perseverance Science and Technology Ltd.；On GL-22M high speed freezing centrifuges
Hai Luxiang instrument centrifuges Instrument Ltd.；The CO2 incubator Heraeus companies of Hera cell 150；Dragon Wellscan
MK3 ELIASA Labsystems companies.
2. experimental method：
It is 2 × 10 to add number of cells6/ ml μ l/ the holes of cell suspension 100, adherent add after purification contain active peptide
INNQFLPYPYYAKPA (1mg/ml) the μ l/ holes of RPMI1640 complete culture solutions (10%FBS) 200 are experimental group, and addition is free of
What the μ l/ holes of RPMI1640 complete culture solutions (10%FBS) 200 of active peptide were cultivated is set to blank group；And experimental group and
Blank group adds LPS to the μ g/ml of final concentration 10 when 24h is arrived in culture；Continue to cultivate to 48h, cell culture fluid is abandoned in suction.PBS
37 DEG C of μ l/ holes of dimethyl diaminophenazine chloride dye liquor 80 are added behind clean-out opening bottom, is inhaled after 10 minutes and abandons dye liquor, with PBS twice after, add per hole
Enter 150 μ l cell pyrolysis liquid (glacial acetic acid：Absolute ethyl alcohol=1:1, v/v).After 4 DEG C of dissolvings overnight, determine and inhale under wavelength 540nm
Shading value (OD540).
3. experimental result and analysis：
The biologically active polypeptide INNQFLPYPYYAKPA of table 1 promotees the measure of macrophage phagocytosis dimethyl diaminophenazine chloride ability
| Experiment packet | Inflammation group absorbance (OD540) |
| Blank group | 0.1031±0.0846 |
| Experimental group | 0.1409±0.0237** |
Note：*, compared with negative control, there is significant difference (P ＜ 0.05)
*, compared with negative control group, there is significant difference (P ＜ 0.01)
Experimental result is shown in Table 1, compared with cell blank, adds 1mg/ml biologically active polypeptides INNQFLPYPYYAKPA
Inflammation group macrophage phagocytosis dimethyl diaminophenazine chloride ability substantially increase, and compared with cell blank group, there is significant difference (P
＜ 0.01).Illustrate that biologically active polypeptide INNQFLPYPYYAKPA swallows in the case where there is inflammation generation to macrophages in vitro
Dimethyl diaminophenazine chloride ability has significant facilitation.
The activity of fighting against senium experiment of the biologically active peptide of embodiment 3
First, biologically active polypeptide INNQFLPYPYYAKPA 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 INNQFLPYPYYAKPA 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
INNQFLPYPYYAKPA biologically active peptides-corn culture medium respectively containing 0.05mg/ml, 0.5mg/ml, 1mg/ml.Every 2
It changes fresh culture once, observes daily and records the death toll of different sexes drosophila, untill drosophila is all dead.
Drosophila survival curve is drawn, and calculates the average life span of different sexes drosophila and maximum life span (takes 5 drosophilas of last death
Counted).
3. experimental result and analysis：
This experiment is as follows to the result of study of the life span of drosophila melanogaster of feeding various concentrations biologically active peptide：Can be with from Fig. 5 (A)
It was found that for blank control group Male Drosophila, feeding concentration is that 0.05mg/ml INNQFLPYPYYAKPA does not have
The survival rate of Male Drosophila is significantly changed, and when peptide concentration reaches 0.5mg/ml and 1mg/ml, same time point, Male Drosophila
Survival rate be significantly improved.From Fig. 5 (B), relative to blank control group female Drosophila, feeding concentration be 0.5mg/ml and
During 1mg/ml, in same time point, the survival rate of female Drosophila increases, but result difference unobvious.
Influence situations of the table 2-1 INNQFLPYPYYAKPA to the Male Drosophila life-span
Note：* sign has significant difference (P compared with blank control group<0.05)；Similarly hereinafter.
Influence situations of the table 2-2 INNQFLPYPYYAKPA to the female Drosophila life-span
It was found from from table 2-1, 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 16.59% and 8.5%, 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
2-2 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 INNQFLPYPYYAKPA can improve drosophila under finite concentration
Average life span and MaLS, but it is relevant with concentration and sex.This phenomenon related to tested material concentration, strain be probably because
For INNQFLPYPYYAKPA participate in drosophila part biological metabolism, or by improve drosophila organize antioxidant system come
Reach the effect for extending 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 property
Other difference, it may be possible to because female Drosophila inherently has certain conservative and the resistance to external environment, so
INNQFLPYPYYAKPA is to female Drosophila life and unobvious.
2nd, biologically active polypeptide INNQFLPYPYYAKPA improves the experiment of drosophila fertility
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 INNQFLPYPYYAKPA 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：
The drosophila adult newly to sprout wings in 8 hours is collected, its male and female is separately fed, concentration is separately added into culture medium is
0mg/ml, 0.05mg/ml, 0.5mg/ml, 1mg/ml INNQFLPYPYYAKPA solution, continuous culture 12 days.Collect within 13rd day
The adult drosophila cultivated under same concentrations is simultaneously transferred in new Nostoc commune Vanch bottle, and each blake bottle ensures 1 female and 2 heros
Property (every group 5 bottles), gives accurate 24 hours for every bottle and is laid eggs.Parent drosophila is transferred to new Nostoc commune Vanch bottle after spawning
In, old blake bottle continues breeding culture, counts progeny size, METHOD FOR CONTINUOUS DETERMINATION 7 days after larva sprouts wings, and be repeated 3 times.
3. experimental result and analysis：
The reproductive capacity measurement result of table 3
From table 3 it can be seen that low concentration experimental group reproductive capacity does not produce conspicuousness change, but middle dosage compared with control group
Experimental group and the reproductive capacity of high dose experimental group drosophila are significantly increased (P compared with blank control group<0.05).Illustrate certain dense
The INNQFLPYPYYAKPA of degree can promote the reproductive capacity of drosophila.Originally test result indicates that, the extension of life span of drosophila melanogaster is
The result that INNQFLPYPYYAKPA is directly acted on, rather than INNQFLPYPYYAKPA are given birth to by reducing two level caused by reproductive capacity
Manage effect.Also illustrate that INNQFLPYPYYAKPA is safe to drosophila simultaneously, without toxic hazard.
3rd, the experiment that biologically active polypeptide INNQFLPYPYYAKPA 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
INNQFLPYPYYAKPA。
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 INNQFLPYPYYAKPA biologically active peptides-corn culture medium.Change fresh culture within every 2 days
Once, after raising 30 days, every group weighs drosophila 40mg, adds 0.5ml physiological saline, grinds and is homogenized in ice bath, the interval 10s seconds,
It is repeated 3 times, homogenate is made, every group of drosophila SOD activity and MDA levels is determined according to kit explanation.Examined using MDA
The levels of lipid peroxidation product MDA in test agent box detection drosophila body, the wavelength of spectrophotometer is 532nm.
3. experimental result and analysis：
Influences of the INNQFLPYPYYAKPA of table 4 to drosophila SOD, MDA
As can be known from Table 4, 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 4,
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
INNQFLPYPYYAKPA is favorably improved the vigor of the Antioxidant Enzymes in body body, so as to effectively improve the antioxygen of body
Change ability, reduce body is stimulated by the bad factor, so as to reduce organism aging process, aging and sick probability, all in all, for
The effect of Male Drosophila 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 panda dairy industry Group Plc；Zhejiang Hui Tai life and healths Science and Technology Ltd.
<120>A kind of biologically active polypeptide INNQFLPYPYYAKPA and its preparation method and application
<160> 3
<170> SIPOSequenceListing 1.0
<210> 1
<211> 15
<212> PRT
<213>Artificial sequence (Artificial Sequence)
<400> 1
Ile Asn Asn Gln Phe Leu Pro Tyr Pro Tyr Tyr Ala Lys Pro Ala
1 5 10 15
<210> 2
<211> 45
<212> DNA
<213>Artificial sequence (Artificial Sequence)
<400> 2
attaataatc aatttctgcc atacccatat tatgcaaagc cagct 45
<210> 3
<211> 190
<212> PRT
<213>Artificial sequence (Artificial Sequence)
<400> 3
Met Met Lys Ser Phe Phe Leu Val Val Thr Ile Leu Ala Leu Thr Leu
1 5 10 15
Pro Phe Leu Gly Ala Gln Glu Gln Asn Gln Glu Gln Pro Ile Arg Cys
20 25 30
Glu Lys Asp Glu Arg Phe Phe Ser Asp Lys Ile Ala Lys Tyr Ile Pro
35 40 45
Ile Gln Tyr Val Leu Ser Arg Tyr Pro Ser Tyr Gly Leu Asn Tyr Tyr
50 55 60
Gln Gln Lys Pro Val Ala Leu Ile Asn Asn Gln Phe Leu Pro Tyr Pro
65 70 75 80
Tyr Tyr Ala Lys Pro Ala Ala Val Arg Ser Pro Ala Gln Ile Leu Gln
85 90 95
Trp Gln Val Leu Ser Asn Thr Val Pro Ala Lys Ser Cys Gln Ala Gln
100 105 110
Pro Thr Thr Met Ala Arg His Pro His Pro His Leu Ser Phe Met Ala
115 120 125
Ile Pro Pro Lys Lys Asn Gln Asp Lys Thr Glu Ile Pro Thr Ile Asn
130 135 140
Thr Ile Ala Ser Gly Glu Pro Thr Ser Thr Pro Thr Thr Glu Ala Val
145 150 155 160
Glu Ser Thr Val Ala Thr Leu Glu Asp Ser Pro Glu Val Ile Glu Ser
165 170 175
Pro Pro Glu Ile Asn Thr Val Gln Val Thr Ser Thr Ala Val
180 185 190
Claims (10)
1. a kind of biologically active polypeptide INNQFLPYPYYAKPA, it is characterised in that its amino acid sequence is Ile-Asn-Asn-
Gln-Phe-Leu-Pro-Tyr-Pro-Tyr-Tyr-Ala-Lys-Pro-Ala。
A kind of 2. biologically active polypeptide INNQFLPYPYYAKPA according to claim 1, it is characterised in that the biology
Active peptides are milk-derived.
3. encode the nucleotide fragments of biologically active polypeptide INNQFLPYPYYAKPA described in claim 1, it is characterised in that institute
State the sequence such as SEQ ID NO of nucleotide fragments：Shown in 2.
4. biologically active polypeptide INNQFLPYPYYAKPA as claimed in claim 1 preparation method, it is characterised in that pass through base
Because the method for engineering is artificial synthesized, or directly obtained by the method isolated and purified from dairy products, or directly closed by chemistry
Into preparation.
5. biologically active polypeptide INNQFLPYPYYAKPA as claimed in claim 1 application, it is characterised in that the biology is living
Property polypeptide INNQFLPYPYYAKPA prepare with the food of immunoloregulation function, health products, medicine or cosmetics should
With.
6. biologically active polypeptide INNQFLPYPYYAKPA as claimed in claim 1 application, it is characterised in that the biology is living
Property polypeptide INNQFLPYPYYAKPA preparing with the application in the food of anti-senescence function, health products or medicine.
7. biologically active polypeptide INNQFLPYPYYAKPA as claimed in claim 1 application, it is characterised in that the biology is living
Property polypeptide INNQFLPYPYYAKPA in the food with immunoloregulation function and anti-senescence function, health products or medicine is prepared
Application.
8. a kind of immunological regulation product, it is characterised in that including biologically active polypeptide as claimed in claim 1
INNQFLPYPYYAKPA or described biologically active polypeptides INNQFLPYPYYAKPA derivative；Described immunological regulation product bag
Include immunological regulation food, immunological regulation health products, immunoregulation medicament or immunological regulation cosmetics；The biologically active polypeptide
INNQFLPYPYYAKPA derivative, refer on biologically active polypeptide INNQFLPYPYYAKPA amino acid side groups,
Aminoterminal or c-terminus carry out hydroxylating, carboxylated, be carbonylated, methylate, acetylation, phosphorylation, esterification or glycosylation modified,
Obtained polypeptide derivative.
9. a kind of anti-aging product, it is characterised in that including biologically active polypeptide as claimed in claim 1
INNQFLPYPYYAKPA or described biologically active polypeptides INNQFLPYPYYAKPA derivative；Described anti-aging product includes
Antisenility cistanche food, antisenescence health product or antiaging agent；The derivative of the biologically active polypeptide INNQFLPYPYYAKPA,
Refer on biologically active polypeptide INNQFLPYPYYAKPA amino acid side groups, aminoterminal or c-terminus carry out hydroxylating,
Carboxylated, be carbonylated, methylate, acetylation, phosphorylation, esterification or glycosylation modified, obtained polypeptide derivative.
10. a kind of product with immunoloregulation function and anti-senescence function, it is characterised in that including as claimed in claim 1
Biologically active polypeptide INNQFLPYPYYAKPA or described biologically active polypeptides INNQFLPYPYYAKPA derivative；With immune
The product of regulatory function and anti-senescence function includes food, health products or medicine；The biologically active polypeptide
INNQFLPYPYYAKPA derivative, refer on biologically active polypeptide INNQFLPYPYYAKPA amino acid side groups,
Aminoterminal or c-terminus carry out hydroxylating, carboxylated, be carbonylated, methylate, acetylation, phosphorylation, esterification or glycosylation modified,
Obtained polypeptide derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711250938.9A CN107759681A (en) | 2017-12-01 | 2017-12-01 | A kind of biologically active polypeptide INNQFLPYPYYAKPA and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711250938.9A CN107759681A (en) | 2017-12-01 | 2017-12-01 | A kind of biologically active polypeptide INNQFLPYPYYAKPA and its preparation method and application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107759681A true CN107759681A (en) | 2018-03-06 |
Family
ID=61277124
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711250938.9A Pending CN107759681A (en) | 2017-12-01 | 2017-12-01 | A kind of biologically active polypeptide INNQFLPYPYYAKPA and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107759681A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108341855A (en) * | 2018-05-09 | 2018-07-31 | 浙江熊猫乳业集团股份有限公司 | A kind of biologically active polypeptide ADVKIGNDTVIEGN and its preparation method and application |
| CN108623669A (en) * | 2018-05-02 | 2018-10-09 | 扬州大学 | Immune-active peptides and its enrichment method and application in a kind of acidified milk |
| CN112646023A (en) * | 2021-01-21 | 2021-04-13 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide with amino acid structure VNVVPTFGKKKGP, 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 |
| CN112724239A (en) * | 2021-01-22 | 2021-04-30 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide with amino acid structure NKELDPVQKLFVDKIREYK 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 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107236031A (en) * | 2017-07-06 | 2017-10-10 | 浙江辉肽生命健康科技有限公司 | A kind of biologically active polypeptide PMIGVNQELAY and its preparation method and application |
-
2017
- 2017-12-01 CN CN201711250938.9A patent/CN107759681A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107236031A (en) * | 2017-07-06 | 2017-10-10 | 浙江辉肽生命健康科技有限公司 | A kind of biologically active polypeptide PMIGVNQELAY and its preparation method and application |
Non-Patent Citations (2)
| Title |
|---|
| 于洋等: "乳源生物活性肽研究进展", 《食品与发酵工艺》 * |
| 高扬等: "乳源性小肽QEPV的抗衰老功能研究", 《中国乳品工业》 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108623669A (en) * | 2018-05-02 | 2018-10-09 | 扬州大学 | Immune-active peptides and its enrichment method and application in a kind of acidified milk |
| CN108623669B (en) * | 2018-05-02 | 2021-07-09 | 扬州大学 | Immune active peptide in fermented milk and enrichment method and application thereof |
| CN108341855A (en) * | 2018-05-09 | 2018-07-31 | 浙江熊猫乳业集团股份有限公司 | A kind of biologically active polypeptide ADVKIGNDTVIEGN and its preparation method and application |
| 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 |
| CN112646023A (en) * | 2021-01-21 | 2021-04-13 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide with amino acid structure VNVVPTFGKKKGP, 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 |
| CN112724239A (en) * | 2021-01-22 | 2021-04-30 | 浙江辉肽生命健康科技有限公司 | Bioactive peptide with amino acid structure NKELDPVQKLFVDKIREYK and application thereof |
| CN112724239B (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 NKELDPVQKLFVDKIREYK and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107759681A (en) | A kind of biologically active polypeptide INNQFLPYPYYAKPA and its preparation method and application | |
| CN108794598A (en) | A kind of biologically active polypeptide NARIQDNLYLAV and its preparation method and application | |
| CN107176995A (en) | A kind of biologically active polypeptide SKVLPVPEKAVPYPQ and its preparation method and application | |
| CN107200780A (en) | A kind of biologically active polypeptide LVYPFPG and its preparation method and application | |
| CN108017701A (en) | A kind of biologically active polypeptide FPKYPVEPF and its preparation method and application | |
| CN109160944A (en) | A kind of biologically active polypeptide ATAVPIIFF and its preparation method and application | |
| CN108017702A (en) | A kind of biologically active polypeptide FPPQSVLS and its preparation method and application | |
| CN107814839A (en) | A kind of biologically active polypeptide PIGSENSEKTTMPL and its preparation method and application | |
| CN108794593A (en) | A kind of biologically active polypeptide GSVNDVQ and its preparation method and application | |
| CN107840880A (en) | A kind of biologically active polypeptide GLNYYQQKPVA and its preparation method and application | |
| CN108997483A (en) | A kind of biologically active polypeptide DQDLVLI and its preparation method and application | |
| CN107746428A (en) | A kind of biologically active polypeptide DERFFSDKIA and its preparation method and application | |
| CN108341855A (en) | A kind of biologically active polypeptide ADVKIGNDTVIEGN and its preparation method and application | |
| CN108794602A (en) | A kind of biologically active polypeptide PNIMVIQH and its preparation method and application | |
| CN108794604A (en) | A kind of biologically active polypeptide SVAPAAAGIN and its preparation method and application | |
| CN108558991A (en) | A kind of biologically active polypeptide GIQDPKEP and its preparation method and application | |
| CN107840882A (en) | A kind of biologically active polypeptide DIPNPIGSE and its preparation method and application | |
| CN108794605A (en) | A kind of biologically active polypeptide SRPETSG and its preparation method and application | |
| CN107827972A (en) | A kind of biologically active polypeptide SPEVIESPPEIN and its preparation method and application | |
| CN108794600A (en) | A kind of biologically active polypeptide SNLIEVT and its preparation method and application | |
| CN107903316A (en) | A kind of biologically active polypeptide LPYPYYA and its preparation method and application | |
| CN107903314A (en) | A kind of biologically active polypeptide EVIESPPEINTV and its preparation method and application | |
| CN107880107A (en) | A kind of biologically active polypeptide QVLSNTVPA and its preparation method and application | |
| CN107880108A (en) | A kind of biologically active polypeptide SFSDIPNPIGSE and its preparation method and application | |
| CN108794588A (en) | A kind of biologically active polypeptide FDPTLHQ and its preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information | ||
| CB02 | Change of applicant information |
Address after: 325800 LITE-ON East Road, Ling Xi Town, Cangnan County, Zhejiang 650-668 Applicant after: Panda Dairy Group Limited by Share Ltd Applicant after: Zhejiang peptide life health science and Technology Co Ltd Address before: 325800 LITE-ON East Road, Ling Xi Town, Cangnan County, Wenzhou, Zhejiang 650-668 Applicant before: ZHEJIANG PANDA DAIRY CORPORATION Applicant before: Zhejiang peptide life health science and Technology Co Ltd |
|
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180306 |