CN112480232B - 一种生物活性肽vsladlqndevafr及其制备方法和应用 - Google Patents
一种生物活性肽vsladlqndevafr及其制备方法和应用 Download PDFInfo
- Publication number
- CN112480232B CN112480232B CN202011467487.6A CN202011467487A CN112480232B CN 112480232 B CN112480232 B CN 112480232B CN 202011467487 A CN202011467487 A CN 202011467487A CN 112480232 B CN112480232 B CN 112480232B
- Authority
- CN
- China
- Prior art keywords
- vsladlqndevafr
- biologically active
- active peptide
- peptide
- val
- 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.)
- Active
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 91
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 230000000975 bioactive effect Effects 0.000 claims abstract description 38
- 230000035755 proliferation Effects 0.000 claims abstract description 16
- 238000000338 in vitro Methods 0.000 claims abstract description 13
- 210000002540 macrophage Anatomy 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 8
- 229940079593 drug Drugs 0.000 claims abstract description 7
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 2
- 230000008975 immunomodulatory function Effects 0.000 claims description 7
- 238000003786 synthesis reaction Methods 0.000 claims description 7
- 108091033319 polynucleotide Proteins 0.000 claims description 2
- 239000002157 polynucleotide Substances 0.000 claims description 2
- 102000040430 polynucleotide Human genes 0.000 claims description 2
- 210000004698 lymphocyte Anatomy 0.000 abstract description 19
- 230000006870 function Effects 0.000 abstract description 14
- 102000004169 proteins and genes Human genes 0.000 abstract description 9
- 108090000623 proteins and genes Proteins 0.000 abstract description 9
- 235000013305 food Nutrition 0.000 abstract description 8
- 238000002474 experimental method Methods 0.000 abstract description 5
- 230000036541 health Effects 0.000 abstract description 4
- 230000003832 immune regulation Effects 0.000 abstract description 4
- 230000036039 immunity Effects 0.000 abstract description 4
- 230000001737 promoting effect Effects 0.000 abstract description 3
- 238000011161 development Methods 0.000 abstract description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 27
- 241000699666 Mus <mouse, genus> Species 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 12
- 238000000034 method Methods 0.000 description 11
- 239000012980 RPMI-1640 medium Substances 0.000 description 10
- 150000001413 amino acids Chemical group 0.000 description 10
- 239000013642 negative control Substances 0.000 description 10
- 230000002519 immonomodulatory effect Effects 0.000 description 9
- 101710131943 40S ribosomal protein S3a Proteins 0.000 description 8
- 102100022600 40S ribosomal protein S3a Human genes 0.000 description 8
- 230000003110 anti-inflammatory effect Effects 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- 229940098773 bovine serum albumin Drugs 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 6
- 239000002158 endotoxin Substances 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- 229920006008 lipopolysaccharide Polymers 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 210000003024 peritoneal macrophage Anatomy 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 210000000952 spleen Anatomy 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 108010077544 Chromatin Proteins 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 206010057249 Phagocytosis Diseases 0.000 description 3
- 230000001464 adherent effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 210000003483 chromatin Anatomy 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000008782 phagocytosis Effects 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 3
- HBOMLICNUCNMMY-KJFJCRTCSA-N 1-[(4s,5s)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1C1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-KJFJCRTCSA-N 0.000 description 2
- 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
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- BXICSAQLIHFDDL-YUMQZZPRSA-N Gly-Lys-Asn Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O BXICSAQLIHFDDL-YUMQZZPRSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 108010047857 aspartylglycine Proteins 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000004807 desolvation Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- USSYUMHVHQSYNA-SLDJZXPVSA-N indolicidin Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)CC1=CNC2=CC=CC=C12 USSYUMHVHQSYNA-SLDJZXPVSA-N 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- 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
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- RLMISHABBKUNFO-WHFBIAKZSA-N Ala-Ala-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O RLMISHABBKUNFO-WHFBIAKZSA-N 0.000 description 1
- KIUYPHAMDKDICO-WHFBIAKZSA-N Ala-Asp-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O KIUYPHAMDKDICO-WHFBIAKZSA-N 0.000 description 1
- VCSABYLVNWQYQE-SRVKXCTJSA-N Ala-Lys-Lys Chemical compound NCCCC[C@H](NC(=O)[C@@H](N)C)C(=O)N[C@@H](CCCCN)C(O)=O VCSABYLVNWQYQE-SRVKXCTJSA-N 0.000 description 1
- VCSABYLVNWQYQE-UHFFFAOYSA-N Ala-Lys-Lys Natural products NCCCCC(NC(=O)C(N)C)C(=O)NC(CCCCN)C(O)=O VCSABYLVNWQYQE-UHFFFAOYSA-N 0.000 description 1
- RMAWDDRDTRSZIR-ZLUOBGJFSA-N Ala-Ser-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O RMAWDDRDTRSZIR-ZLUOBGJFSA-N 0.000 description 1
- QPOARHANPULOTM-GMOBBJLQSA-N Arg-Asn-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N QPOARHANPULOTM-GMOBBJLQSA-N 0.000 description 1
- RIQBRKVTFBWEDY-RHYQMDGZSA-N Arg-Lys-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O RIQBRKVTFBWEDY-RHYQMDGZSA-N 0.000 description 1
- UPALZCBCKAMGIY-PEFMBERDSA-N Asn-Gln-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O UPALZCBCKAMGIY-PEFMBERDSA-N 0.000 description 1
- ORJQQZIXTOYGGH-SRVKXCTJSA-N Asn-Lys-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O ORJQQZIXTOYGGH-SRVKXCTJSA-N 0.000 description 1
- XDGBFDYXZCMYEX-NUMRIWBASA-N Asp-Glu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)N)O XDGBFDYXZCMYEX-NUMRIWBASA-N 0.000 description 1
- KQBVNNAPIURMPD-PEFMBERDSA-N Asp-Ile-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O KQBVNNAPIURMPD-PEFMBERDSA-N 0.000 description 1
- CJUKAWUWBZCTDQ-SRVKXCTJSA-N Asp-Leu-Lys Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O CJUKAWUWBZCTDQ-SRVKXCTJSA-N 0.000 description 1
- XUVTWGPERWIERB-IHRRRGAJSA-N Asp-Pro-Phe Chemical compound N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(O)=O XUVTWGPERWIERB-IHRRRGAJSA-N 0.000 description 1
- GHAHOJDCBRXAKC-IHPCNDPISA-N Asp-Trp-Tyr Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)O)NC(=O)[C@H](CC(=O)O)N GHAHOJDCBRXAKC-IHPCNDPISA-N 0.000 description 1
- MFDPBZAFCRKYEY-LAEOZQHASA-N Asp-Val-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O MFDPBZAFCRKYEY-LAEOZQHASA-N 0.000 description 1
- SFJUYBCDQBAYAJ-YDHLFZDLSA-N Asp-Val-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SFJUYBCDQBAYAJ-YDHLFZDLSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 238000012270 DNA recombination Methods 0.000 description 1
- PODFFOWWLUPNMN-DCAQKATOSA-N Gln-His-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(N)=O)C(O)=O PODFFOWWLUPNMN-DCAQKATOSA-N 0.000 description 1
- SXFPZRRVWSUYII-KBIXCLLPSA-N Gln-Ser-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)N)N SXFPZRRVWSUYII-KBIXCLLPSA-N 0.000 description 1
- UXXIVIQGOODKQC-NUMRIWBASA-N Gln-Thr-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N)O UXXIVIQGOODKQC-NUMRIWBASA-N 0.000 description 1
- BPDVTFBJZNBHEU-HGNGGELXSA-N Glu-Ala-His Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 BPDVTFBJZNBHEU-HGNGGELXSA-N 0.000 description 1
- OAGVHWYIBZMWLA-YFKPBYRVSA-N Glu-Gly-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)NCC(O)=O OAGVHWYIBZMWLA-YFKPBYRVSA-N 0.000 description 1
- GRHXUHCFENOCOS-ZPFDUUQYSA-N Glu-Ile-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CCC(=O)O)N GRHXUHCFENOCOS-ZPFDUUQYSA-N 0.000 description 1
- DCBSZJJHOTXMHY-DCAQKATOSA-N Glu-Pro-Pro Chemical compound OC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DCBSZJJHOTXMHY-DCAQKATOSA-N 0.000 description 1
- SOYWRINXUSUWEQ-DLOVCJGASA-N Glu-Val-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCC(O)=O SOYWRINXUSUWEQ-DLOVCJGASA-N 0.000 description 1
- JBRBACJPBZNFMF-YUMQZZPRSA-N Gly-Ala-Lys Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCCN JBRBACJPBZNFMF-YUMQZZPRSA-N 0.000 description 1
- LLZXNUUIBOALNY-QWRGUYRKSA-N Gly-Leu-Lys Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCCN LLZXNUUIBOALNY-QWRGUYRKSA-N 0.000 description 1
- VEPBEGNDJYANCF-QWRGUYRKSA-N Gly-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCCN VEPBEGNDJYANCF-QWRGUYRKSA-N 0.000 description 1
- FXGRXIATVXUAHO-WEDXCCLWSA-N Gly-Lys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCCN FXGRXIATVXUAHO-WEDXCCLWSA-N 0.000 description 1
- WNZOCXUOGVYYBJ-CDMKHQONSA-N Gly-Phe-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CN)O WNZOCXUOGVYYBJ-CDMKHQONSA-N 0.000 description 1
- RIYIFUFFFBIOEU-KBPBESRZSA-N Gly-Tyr-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=C(O)C=C1 RIYIFUFFFBIOEU-KBPBESRZSA-N 0.000 description 1
- YOTNPRLPIPHQSB-XUXIUFHCSA-N Ile-Arg-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O)N YOTNPRLPIPHQSB-XUXIUFHCSA-N 0.000 description 1
- PDTMWFVVNZYWTR-NHCYSSNCSA-N Ile-Gly-Lys Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@@H](CCCCN)C(O)=O PDTMWFVVNZYWTR-NHCYSSNCSA-N 0.000 description 1
- OWSWUWDMSNXTNE-GMOBBJLQSA-N Ile-Pro-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)O)N OWSWUWDMSNXTNE-GMOBBJLQSA-N 0.000 description 1
- COWHUQXTSYTKQC-RWRJDSDZSA-N Ile-Thr-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N COWHUQXTSYTKQC-RWRJDSDZSA-N 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 108010065920 Insulin Lispro Proteins 0.000 description 1
- 241000588747 Klebsiella pneumoniae Species 0.000 description 1
- HGCNKOLVKRAVHD-UHFFFAOYSA-N L-Met-L-Phe Natural products CSCCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 HGCNKOLVKRAVHD-UHFFFAOYSA-N 0.000 description 1
- KFKWRHQBZQICHA-STQMWFEESA-N L-leucyl-L-phenylalanine Natural products CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KFKWRHQBZQICHA-STQMWFEESA-N 0.000 description 1
- 241000880493 Leptailurus serval Species 0.000 description 1
- QUAAUWNLWMLERT-IHRRRGAJSA-N Leu-Arg-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(C)C)C(O)=O QUAAUWNLWMLERT-IHRRRGAJSA-N 0.000 description 1
- APFJUBGRZGMQFF-QWRGUYRKSA-N Leu-Gly-Lys Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCCN APFJUBGRZGMQFF-QWRGUYRKSA-N 0.000 description 1
- CFZZDVMBRYFFNU-QWRGUYRKSA-N Leu-His-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)NCC(O)=O CFZZDVMBRYFFNU-QWRGUYRKSA-N 0.000 description 1
- KPYAOIVPJKPIOU-KKUMJFAQSA-N Leu-Lys-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O KPYAOIVPJKPIOU-KKUMJFAQSA-N 0.000 description 1
- BJWKOATWNQJPSK-SRVKXCTJSA-N Leu-Met-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N BJWKOATWNQJPSK-SRVKXCTJSA-N 0.000 description 1
- AEDWWMMHUGYIFD-HJGDQZAQSA-N Leu-Thr-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O AEDWWMMHUGYIFD-HJGDQZAQSA-N 0.000 description 1
- 102000008072 Lymphokines Human genes 0.000 description 1
- 108010074338 Lymphokines Proteins 0.000 description 1
- VHFFQUSNFFIZBT-CIUDSAMLSA-N Lys-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCCN)N VHFFQUSNFFIZBT-CIUDSAMLSA-N 0.000 description 1
- ALSRJRIWBNENFY-DCAQKATOSA-N Lys-Arg-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O ALSRJRIWBNENFY-DCAQKATOSA-N 0.000 description 1
- YNNPKXBBRZVIRX-IHRRRGAJSA-N Lys-Arg-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O YNNPKXBBRZVIRX-IHRRRGAJSA-N 0.000 description 1
- TYEJPFJNAHIKRT-DCAQKATOSA-N Lys-Met-Cys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCCN)N TYEJPFJNAHIKRT-DCAQKATOSA-N 0.000 description 1
- INMBONMDMGPADT-AVGNSLFASA-N Lys-Met-Met Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CCCCN)N INMBONMDMGPADT-AVGNSLFASA-N 0.000 description 1
- OEYKVQKYCHATHO-SZMVWBNQSA-N Lys-Trp-Gln Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N OEYKVQKYCHATHO-SZMVWBNQSA-N 0.000 description 1
- IKXQOBUBZSOWDY-AVGNSLFASA-N Lys-Val-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CCCCN)N IKXQOBUBZSOWDY-AVGNSLFASA-N 0.000 description 1
- DTICLBJHRYSJLH-GUBZILKMSA-N Met-Ala-Val Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O DTICLBJHRYSJLH-GUBZILKMSA-N 0.000 description 1
- OSOLWRWQADPDIQ-DCAQKATOSA-N Met-Asp-Leu Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O OSOLWRWQADPDIQ-DCAQKATOSA-N 0.000 description 1
- LPNWWHBFXPNHJG-AVGNSLFASA-N Met-Val-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN LPNWWHBFXPNHJG-AVGNSLFASA-N 0.000 description 1
- YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-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
- 102000001490 Opioid Peptides Human genes 0.000 description 1
- 108010093625 Opioid Peptides Proteins 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- YYRCPTVAPLQRNC-ULQDDVLXSA-N Phe-Arg-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CC1=CC=CC=C1 YYRCPTVAPLQRNC-ULQDDVLXSA-N 0.000 description 1
- KIEPQOIQHFKQLK-PCBIJLKTSA-N Phe-Asn-Ile Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O KIEPQOIQHFKQLK-PCBIJLKTSA-N 0.000 description 1
- OWCLJDXHHZUNEL-IHRRRGAJSA-N Phe-Cys-Val Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(O)=O OWCLJDXHHZUNEL-IHRRRGAJSA-N 0.000 description 1
- SFKOEHXABNPLRT-KBPBESRZSA-N Phe-His-Gly Chemical compound N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)NCC(O)=O SFKOEHXABNPLRT-KBPBESRZSA-N 0.000 description 1
- DOXQMJCSSYZSNM-BZSNNMDCSA-N Phe-Lys-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O DOXQMJCSSYZSNM-BZSNNMDCSA-N 0.000 description 1
- DRVIASBABBMZTF-GUBZILKMSA-N Pro-Ala-Met Chemical compound C[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@@H]1CCCN1 DRVIASBABBMZTF-GUBZILKMSA-N 0.000 description 1
- SMFQZMGHCODUPQ-ULQDDVLXSA-N Pro-Lys-Phe Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O SMFQZMGHCODUPQ-ULQDDVLXSA-N 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- CRJZZXMAADSBBQ-SRVKXCTJSA-N Ser-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CO CRJZZXMAADSBBQ-SRVKXCTJSA-N 0.000 description 1
- SRSPTFBENMJHMR-WHFBIAKZSA-N Ser-Ser-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SRSPTFBENMJHMR-WHFBIAKZSA-N 0.000 description 1
- PIQRHJQWEPWFJG-UWJYBYFXSA-N Ser-Tyr-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(O)=O PIQRHJQWEPWFJG-UWJYBYFXSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- GLQFKOVWXPPFTP-VEVYYDQMSA-N Thr-Arg-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O GLQFKOVWXPPFTP-VEVYYDQMSA-N 0.000 description 1
- UKBSDLHIKIXJKH-HJGDQZAQSA-N Thr-Arg-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O UKBSDLHIKIXJKH-HJGDQZAQSA-N 0.000 description 1
- UHBPFYOQQPFKQR-JHEQGTHGSA-N Thr-Gln-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O UHBPFYOQQPFKQR-JHEQGTHGSA-N 0.000 description 1
- JLNMFGCJODTXDH-WEDXCCLWSA-N Thr-Lys-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O JLNMFGCJODTXDH-WEDXCCLWSA-N 0.000 description 1
- UUSQVWOVUYMLJA-PPCPHDFISA-N Thr-Lys-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O UUSQVWOVUYMLJA-PPCPHDFISA-N 0.000 description 1
- QFEYTTHKPSOFLV-OSUNSFLBSA-N Thr-Met-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H]([C@@H](C)O)N QFEYTTHKPSOFLV-OSUNSFLBSA-N 0.000 description 1
- YRJOLUDFVAUXLI-GSSVUCPTSA-N Thr-Thr-Asp Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(O)=O YRJOLUDFVAUXLI-GSSVUCPTSA-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
- BIWVVOHTKDLRMP-ULQDDVLXSA-N Tyr-Pro-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O BIWVVOHTKDLRMP-ULQDDVLXSA-N 0.000 description 1
- 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
- SCBITHMBEJNRHC-LSJOCFKGSA-N Val-Asp-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)O)N SCBITHMBEJNRHC-LSJOCFKGSA-N 0.000 description 1
- QHFQQRKNGCXTHL-AUTRQRHGSA-N Val-Gln-Glu Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O QHFQQRKNGCXTHL-AUTRQRHGSA-N 0.000 description 1
- BRPKEERLGYNCNC-NHCYSSNCSA-N Val-Glu-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N BRPKEERLGYNCNC-NHCYSSNCSA-N 0.000 description 1
- RWOGENDAOGMHLX-DCAQKATOSA-N Val-Lys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C(C)C)N RWOGENDAOGMHLX-DCAQKATOSA-N 0.000 description 1
- IEBGHUMBJXIXHM-AVGNSLFASA-N Val-Lys-Met Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)O)N IEBGHUMBJXIXHM-AVGNSLFASA-N 0.000 description 1
- MNSSBIHFEUUXNW-RCWTZXSCSA-N Val-Thr-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N MNSSBIHFEUUXNW-RCWTZXSCSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 108010044940 alanylglutamine Proteins 0.000 description 1
- 108010087924 alanylproline Proteins 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 108010092854 aspartyllysine Proteins 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 230000006315 carbonylation Effects 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- 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 1
- 235000021240 caseins Nutrition 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000000212 effect on lymphocytes Effects 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 1
- 108010078144 glutaminyl-glycine Proteins 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 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
- 108010015792 glycyllysine Proteins 0.000 description 1
- 108010045383 histidyl-glycyl-glutamic acid Proteins 0.000 description 1
- 235000021244 human milk protein Nutrition 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 1
- 108010044056 leucyl-phenylalanine Proteins 0.000 description 1
- 108010064235 lysylglycine Proteins 0.000 description 1
- 108010017391 lysylvaline Proteins 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 108010068488 methionylphenylalanine Proteins 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 239000003399 opiate peptide Substances 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 108010051242 phenylalanylserine Proteins 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 238000005173 quadrupole mass spectroscopy Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 108010061238 threonyl-glycine Proteins 0.000 description 1
- 238000001269 time-of-flight mass spectrometry Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000006433 tumor necrosis factor production Effects 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
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
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
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
-
- 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)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Food Science & Technology (AREA)
- Dermatology (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Mycology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
本发明涉及蛋白领域，具体涉及一种生物活性肽VSLADLQNDEVAFR及其制备方法和应用，生物活性肽VSLADLQNDEVAFR的氨基酸序列为Val‑Ser‑Leu‑Ala‑Asp‑Leu‑Gln‑Asn‑Asp‑Glu‑Val‑Ala‑Phe‑Arg。经过体外免疫调节功能实验，证明生物活性肽VSLADLQNDEVAFR具有很好的免疫调节功能。本发明的生物活性肽VSLADLQNDEVAFR具有显著促进淋巴细胞增殖的能力，能够提高机体的免疫力，同时对体外巨噬细胞增殖有显著促进作用，可提高生命的质量，对开发具有免疫调节功能的食品、保健品和药物具有十分重要的意义。
Description
技术领域
本发明涉及蛋白领域，尤其是涉及一种生物活性肽VSLADLQNDEVAFR及其制备方法和应用。
背景技术
近年来，生物活性肽已经成为人们耳熟能详的一个词语。因其具有很多潜在的生物功能，所以引起人们越来越多的关注，成为科学研究的热点之一。目前很多生物活性肽的有益效果也已经得到了很好的证明，如抗癌、降血压、抗菌、降胆固醇、抗糖尿病等等特性。当前最权威的生物活性肽数据库BIOPEP-UMW中已报告了3000多个不同的生物活性肽。
目前对于生物活性肽的研究多集中于食物衍生多肽，对非食物衍生多肽研究和报道较少。且已经有研究结果证实，与食物衍生的生物活性肽相比，非食物衍生的生物活性肽具有更高的亲和力并能有效发挥其生物活性功能。淋巴细胞是免疫系统的中央调节细胞，其大部分功能是由一组被称为淋巴因子的小分子多肽介导的。这些小分子多肽的表达和分泌均是由于抗原刺激的细胞激活而诱导。所以淋巴细胞是动物机体内产生免疫调节肽的主要来源。
免疫调节肽是继阿片肽发现后首次从乳中获得并证明其生理活性的一类生物活性肽。1981年Jolles等人首次发现，利用胰蛋白酶水解人乳蛋白，可以得到一个氨基酸序列为Val-Glu-Pro-Ile-Pro-Tyr的六肽，体外实验证明该肽能够增强小鼠腹腔巨噬细胞对绵羊红细胞的吞噬作用。Migliore-Samour等人发现来自酪蛋白的六肽Thr-Thr-Met-Pro-Leu-Trp能够刺激绵羊血红细胞对小鼠腹膜巨噬细胞的吞噬作用以及增强对于肺炎克雷伯菌的抵抗，具有抗炎功能。李素萍等人用合成的小鼠骨髓巨噬细胞来与源肽（PGPIPN）饲喂大鼠发现大鼠腹腔巨噬细胞的吞噬作用和红细胞相关的抗炎功能有显著的增强。Bowdis等人在研究来源于牛中性粒细胞的13氨基酸肽indolicidin的免疫功能时发现，多肽indolicidin在巨噬细胞样细胞系中抑制LPS诱导的TNF-α产量。
研究表明，免疫调节肽不仅能够增强机体免疫力，刺激机体淋巴细胞的增殖，增强巨噬细胞的吞噬功能，促进细胞因子的释放、促进巨噬细胞一氧化氮诱生量的增加、提高机体抵御外界病原体感染的能力，降低机体发病率，而且不会引起机体的免疫排斥反应。
免疫调节肽一般是指具有免疫调节活性的分子量相对较小的小肽。现在公开的免疫调节肽一般是从蛋白质中酶解分离得到或化学方法合成得到的具有特定免疫调节活性的小肽。但是当这些小肽未从蛋白质中酶解分离时，这些蛋白质本身往往是不具备免疫调节活性的。如何从已知氨基酸序列的种类繁多的蛋白质中寻找具有特定功能的生物活性肽，并研究这些多肽的功能是蛋白领域研究的方向之一。
40S ribosomal protein S3a蛋白的氨基酸序列如SEQ ID NO：2所示。目前，现有技术中并没有关于40S ribosomal protein S3a蛋白多肽片段相关功能的研究。
发明内容
本发明的目的在于提供一种生物活性肽VSLADLQNDEVAFR及其制备方法和应用。
本发明的目的可以通过以下技术方案来实现：
本发明第一方面，提供一种生物活性肽VSLADLQNDEVAFR，其氨基酸序列为Val-Ser-Leu-Ala-Asp-Leu-Gln-Asn-Asp-Glu-Val-Ala-Phe-Arg，如SEQ ID NO：1所示。
较优的，所述生物活性肽为小鼠脾脏来源淋巴细胞肽。具体来源于40S ribosomalprotein S3a蛋白，并且为40S ribosomal protein S3a蛋白第69～82位的氨基酸残基。40Sribosomal protein S3a蛋白氨基酸序列如SEQ ID NO：2所示。
40S ribosomal protein S3a蛋白的氨基酸序列以及对应的核苷酸序列为既有技术，编码40S ribosomal protein S3a蛋白第69～82位氨基酸残基的核苷酸片段能编码成熟的生物活性肽VSLADLQNDEVAFR。
较优的，所述生物活性肽具有抗炎功能和免疫调节功能。
本发明还提供编码所述生物活性肽VSLADLQNDEVAFR的多核苷酸。
本发明第二方面，提供了所述生物活性肽VSLADLQNDEVAFR的制备方法，可以通过基因工程的方法人工合成，可以从细胞中通过分离纯化的方法直接获得，可以直接通过化学合成制备。
通过基因工程的方法人工合成所述生物活性肽VSLADLQNDEVAFR是本领域技术人员能够实现的技术方案，例如可以是以DNA重组技术为基础，通过合适的DNA模板来控制多肽的序列合成。
关于从细胞中通过分离纯化的方法直接获得的方式可以为：基于给定的生物活性肽VSLADLQNDEVAFR的氨基酸序列，采用生物学技术上常规的酶解、纯化方法从小鼠脾脏来源淋巴细胞获得所述生物活性肽VSLADLQNDEVAFR。
本发明第三方面，提供了所述生物活性肽VSLADLQNDEVAFR在制备具有抗炎功能的药物或化妆品中的应用。
本发明第四方面，提供了所述生物活性肽VSLADLQNDEVAFR在制备具有免疫调节功能的食物或药物中的应用。
进一步地，所述生物活性肽VSLADLQNDEVAFR在制备促进淋巴细胞增殖的药物中的应用。
进一步地，所述生物活性肽VSLADLQNDEVAFR在制备促进体外巨噬细胞增殖的的药物中的应用。
本发明第五方面，提供了一种抗炎产品，包括所述生物活性肽VSLADLQNDEVAFR或所述生物活性肽VSLADLQNDEVAFR的衍生物；所述的抗炎产品包括抗炎药物或抗炎化妆品。
本发明第六方面，提供了一种具有免疫调节功能的产品，包括所述生物活性肽VSLADLQNDEVAFR或所述生物活性肽VSLADLQNDEVAFR的衍生物；所述具有免疫调节功能的产品包括具有免疫调节功能的食品或具有免疫调节功能的药物。
所述生物活性肽VSLADLQNDEVAFR的衍生物是指具有与所述生物活性肽VSLADLQNDEVAFR相同的活性或更优的活性。
所述生物活性肽VSLADLQNDEVAFR的衍生物，是指在生物活性肽VSLADLQNDEVAFR的氨基酸侧链基团上、氨基端或羧基端进行羟基化、羧基化、羰基化、甲基化、乙酰化、磷酸化、酯化或糖基化等修饰，得到的生物活性肽衍生物。
本发明生物活性肽VSLADLQNDEVAFR的有益效果为：本发明生物活性肽VSLADLQNDEVAFR具有较好的抗炎活性；本发明的生物活性肽VSLADLQNDEVAFR具有显著促进小鼠淋巴细胞增殖的能力，能够提高机体的免疫力，同时对体外巨噬细胞增殖有显著促进作用，可提高生命的质量，对开发具有免疫调节功能的食品、保健品和药物具有十分重要的意义。
附图说明
图1：质荷比为788.9001的片段的一级质谱图（m/z= 788.9001）；
图2：质荷比为788.9001的片段的二级质谱图和生物活性肽az、by断裂情况；
具体实施方式
在进一步描述本发明具体实施方案之前，应理解，本发明的保护范围不局限于下述特定的具体实施方案；还应当理解，本发明实施例中使用的术语是为了描述特定的具体实施方案，而不是为了限制本发明的保护范围。
当实施例给出数值范围时，应理解，除非本发明另有说明，每个数值范围的两个端点以及两个端点之间任何一个数值均可选用。除非另外定义，本发明中使用的所有技术和科学术语与本技术领域技术人员通常理解的意义相同。除实施例中使用的具体方法、设备、材料外，根据本技术领域的技术人员对现有技术的掌握及本发明的记载，还可以使用与本发明实施例中所述的方法、设备、材料相似或等同的现有技术的任何方法、设备和材料来实现本发明。
除非另外说明，本发明中所公开的实验方法、检测方法、制备方法均采用本技术领域常规的分子生物学、生物化学、染色质结构和分析、分析化学、细胞培养、重组DNA技术及相关领域的常规技术。这些技术在现有文献中已有完善说明，具体可参见Sambrook等MOLECULAR CLONING ：A LABORATORY MANUAL，Second edition，Cold Spring HarborLaboratory Press，1989 and Third edition，2001 ；Ausubel 等，CURRENT PROTOCOLS INMOLECULAR BIOLOGY，John Wiley & Sons，New York，1987 and periodic updates ；theseries METHODS IN ENZYMOLOGY，Academic Press，San Diego ；Wolffe，CHROMATINSTRUCTURE AND FUNCTION，Third edition，Academic Press，San Diego，1998 ；METHODSIN ENZYMOLOGY，Vol.304，Chromatin (P.M.Wassarman and A.P.Wolffe，eds.)，AcademicPress，San Diego，1999 ； 和METHODS IN MOLECULAR BIOLOGY，Vol.119，ChromatinProtocols(P.B.Becker，ed.)Humana Press，Totowa，1999等。
下面结合附图和具体实施例对本发明进行详细说明。
实施例1 生物活性肽VSLADLQNDEVAFR的人工合成
一、生物活性肽的合成
人工合成生物活性肽VSLADLQNDEVAFR。
二、生物活性肽的确认
1）UPLC分析
UPLC条件如下：
仪器：Waters ACQUITY UPLC超高效液相、电喷雾、四级杆、飞行时间质谱仪
色谱柱规格：BEH C18 色谱柱
流速：0.4mL/min
温度：50℃
紫外检测波长：210nm
进样量：2μL
梯度条件：A液：含有0.1%甲酸（v/v）的水，B液：含有0.1%甲酸（v/v）的乙腈
Time(min) %A %B
0 95.0 5.0
1.50 80.0 20.0
3.50 60.0 40.0
5.00 40.0 60.0
7.00 15.0 85.0
8.00 0.0 100.0
11.00 0.0 100.0
11.50 95.0 5.0
13.00 95.0 5.0
2）质谱分析
质谱条件如下：
离子方式：ES+
质量范围（m/z）：100、1000
毛细管电压（Capillary）（kV）：3.0
采样锥（V）：35.0
离子源温度（℃）：115
去溶剂温度（℃）：350
去溶剂气流（L/hr）：700.0
碰撞能量（eV）：4.0
扫描时间（sec）：0.25
内扫描时间（sec）：0.02
根据以上分析方法，利用超高效液相、电喷雾、四级杆、飞行时间质谱，对生物活性肽VSLADLQNDEVAFR进行色谱分析和质谱分析。生物活性肽VSLADLQNDEVAFR一级质谱图如图1所示，提取峰的二级质谱图和az、by断裂情况如图2所示，可得此峰的生物活性肽质荷比为788.9001，保留时间是48.65 min。
3）结果
由图2可知，根据az、by断裂的情况，经过 Mascot 软件分析计算，得到质荷比788.9001的片段序列为Val、Ser、Leu、Ala、Asp、Leu、Gln、Asn、Asp、Glu、Val、Ala、Phe、Arg（VSLADLQNDEVAFR），记为SEQ ID NO：1。该片段与40S ribosomal protein S3a蛋白第69～82位的残基序列相对应，40S ribosomal protein S3a蛋白氨基酸序列的GenBank编号为AAH81451.1，序列见SEQ ID NO：2。
实施例2 生物活性肽的免疫活性实验
一、生物活性肽VSLADLQNDEVAFR的体外淋巴细胞增殖能力实验(MTT法)
1. 实验材料与仪器：
试剂与材料：实验动物 balb/c小鼠（雄性6-8周龄，上海交通大学农业与生物学院动物实验中心）；实施例1获得的小鼠脾脏淋巴细胞来源生物活性肽VSLADLQNDEVAFR；小鼠淋巴细胞提取液（购自索来宝公司）；RPMI1640培养基（购自GIBCO公司）；3-(4，5-二甲基噻唑-2)-2，5-二苯基四氮唑溴盐（MTT，购自Amresco公司）；伴刀豆蛋白（ConA，购自Sigma公司）；牛血清白蛋白（BSA，购自Genebase公司）；胃蛋白酶（购自Sigma公司）；胰酶（CorolasePP，购自AB公司）。
仪器设备：LRH-250F生化培养箱，上海恒科技有限公司；GL-22M高速冷冻离心机，上海卢湘仪离心机仪器有限公司；Hera cell 150 CO2 培养箱，Heraeus公司；DragonWellscan MK3酶标仪，Labsystems公司；ALPHA 1-2-LD 真空冷冻干燥机，Christ 公司；超高效液相色谱-四极杆飞行时间质谱仪，waters公司。
2. 实验方法：
无菌条件下取小鼠脾脏，用淋巴细胞提取液提取小鼠淋巴细胞，进行原代培养。用完全RPMI1640培养液将细胞密度调整为2.5×106个/mL。在96孔细胞培养板中依次加入：100μL小鼠淋巴细胞悬液，100μL RPMI1640完全培养液，20μL伴刀豆蛋白，100μL生物活性肽样品。另外，设置空白对照组（pH7.2～7.4，3mol/L的PBS）和阴性对照组（500μg/mL BSA），研究表明其对于体外淋巴细胞增殖没有影响。每组3个平行实验样。在5%CO2 37℃培养箱中培养68h后，无菌条件下每孔加入20μL MTT，继续培养4h，小心弃去上清液，每孔加入100μL二甲基亚砜，37℃生化培养箱孵化10min，摇匀，用酶标仪在570nm处测定吸光值。
体外淋巴细胞增殖能力用刺激指数来表示，计算方法如下：
式中：A1为空白对照在570nm处下的吸光值；A 2为阴性对照组在570nm处下的吸光值，A 3为实验组在570nm处下的吸光值。
3. 实验结果及分析：
表1 生物活性肽VSLADLQNDEVAFR对体外淋巴细胞增殖的影响
注：*号标记为与阴性对照比较，有显著性差异(P＜0.05)。
实验结果见表1。由表1可知，生物活性肽VSLADLQNDEVAFR的刺激指数大于BSA，说明VSLADLQNDEVAFR一定程度上能刺激体外小鼠淋巴细胞的增殖。并且VSLADLQNDEVAFR的刺激指数达到了1.163，和阴性对照组具有显著差异（P<0.05）。因此，可以认定该生物活性肽VSLADLQNDEVAFR具有显著促进小鼠淋巴细胞增殖的能力，可以作为一种具有免疫调节活性的物质添加到保健品中，能够提高人体的免疫力。
二、MTT法测定生物活性肽VSLADLQNDEVAFR的体外巨噬细胞增殖能力实验
1. 实验试剂及仪器
试剂：实验动物 balb/c小鼠（雄性6-8周龄）上海交通大学农业与生物学院动物实验中心；实施例1获得的小鼠脾脏淋巴细胞来源生物活性肽VSLADLQNDEVAFR；3-(4，5-二甲基噻唑-2)-2，5-二苯基四氮唑溴盐（MTT）Amresco公司；LPS（脂多糖） Sigma公司；牛血清白蛋白（Bovine Serum Albumin，BSA） Genebase公司；三联溶解液，含10%SDS、5%异丁醇以及0.012mol/L HCl的水溶液。
仪器设备：LRH-250F生化培养箱 上海恒科技有限公司；GL-22M高速冷冻离心机上海卢湘仪离心机仪器有限公司； Hera cell 150 CO2 培养箱 Heraeus公司；DragonWellscan MK3酶标仪 Labsystems公司。
2. 试验方法：
balb/c小鼠腹腔注射2ml的2%（w/w）灭菌淀粉溶液，连续注射三天，最后一次注射24小时后断颈处死。剥去腹部皮肤，用注射器吸取4℃磷酸盐缓冲液（PBS）反复冲洗腹腔，离心管收集冲洗液后，离心（1000rpm，4℃）10分钟后弃上清，用4℃RPMI1640完全培养液（含10%FBS）洗涤两次，0.2%台盼蓝溶液染色做细胞活力检测，确认采集到的有活力巨噬细胞占95%以上。细胞计数板读数后，调整细胞浓度至合适浓度。
将已吹打至完全悬浮的细胞悬液以合适体积加入96孔细胞培养板，37℃、5%CO2环境下培养4小时后，吸弃孔中液体，用37℃ RPMI1640完全培养液小心清洗细胞培养板孔底，洗去未贴壁的细胞和细胞碎片，得到纯化后的贴壁腹腔巨噬细胞。每孔加入0.2mlRPMI1640完全培养基，实验用小肽样品及LPS事先溶解于培养基后加入，开始细胞培养。
得到纯化后的贴壁腹腔巨噬细胞后，实验组每孔加溶解有生物活性肽VSLADLQNDEVAFR(0.5mg/ml)的RPMI1640完全培养液（10%FBS）200μl/孔，连续培养48h；阴性对照组每孔加溶解有BSA（500μg/mL）的RPMI1640完全培养液（10%FBS）200μl/孔；空白组添加RPMI1640完全培养液（10%FBS）200μl/孔，连续培养48h。并且，实验组、阴性对照组和空白组又分别设正常组和炎症组；炎症组在培养到24h时加入LPS至终浓度为100ng/ml；正常组不加LPS；并且正常组和炎症组在44h时加入5% MTT 20μl/孔；细胞培养达到48h后加入100μl/孔的三联溶解液以终止培养，隔夜溶解后，在波长570nm下用酶标仪测各孔的吸光度值（OD570），生长指数（Growth Indices）的计算公式如下：
生长指数GI=(小肽组OD值-空白培养液OD值)/(空白组OD值-空白培养液OD值)
其中，空白培养液为含10%FBS的RPMI1640完全培养液。
3. 实验结果及分析
表2 生物活性肽VSLADLQNDEVAFR对体外巨噬细胞增殖的影响
| 实验分组 | 正常组GI | 炎症组GI |
| 阴性对照组 | 1 | 1 |
| 生物活性肽样品（0.5mg/ml） | 1.0164±0.0023* | 1.6893±0.0472** |
注：*表示与阴性对照比较，有显著性差异(P ＜0.05)；**表示与阴性对照组比较，有高度显著性差异(P ＜0.01)
实验结果见表2，由表2可知，在添加0.5mg/ml 生物活性肽VSLADLQNDEVAFR的条件下，正常组和炎症组的巨噬细胞均有增殖。但与阴性对照组比较，炎症组的变化(P ＜0.01)比正常组(P ＜0.05)更为显著，说明生物活性肽VSLADLQNDEVAFR对体外巨噬细胞具有显著的增殖作用。
上述的对实施例的描述是为便于该技术领域的普通技术人员能理解和使用发明。熟悉本领域技术的人员显然可以容易地对这些实施例做出各种修改，并把在此说明的一般原理应用到其他实施例中而不必经过创造性的劳动。因此，本发明不限于上述实施例，本领域技术人员根据本发明的揭示，不脱离本发明范畴所做出的改进和修改都应该在本发明的保护范围之内。
序列表
<110> 上海交通大学,浙江辉肽生命健康科技有限公司
<120> 一种生物活性肽VSLADLQNDEVAFR及其制备方法和应用
<160> 2
<170> SIPOSequenceListing 1.0
<210> 1
<211> 14
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 1
Val Ser Leu Ala Asp Leu Gln Asn Asp Glu Val Ala Phe Arg
1 5 10
<210> 2
<211> 264
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 2
Met Ala Val Gly Lys Asn Lys Arg Leu Thr Lys Gly Gly Lys Lys Gly
1 5 10 15
Ala Lys Lys Lys Val Val Asp Pro Phe Ser Lys Lys Asp Trp Tyr Asp
20 25 30
Val Lys Ala Pro Ala Met Phe Asn Ile Arg Asn Ile Gly Lys Thr Leu
35 40 45
Val Thr Arg Thr Gln Gly Thr Lys Ile Ala Ser Asp Gly Leu Lys Gly
50 55 60
Arg Val Phe Glu Val Ser Leu Ala Asp Leu Gln Asn Asp Glu Val Ala
65 70 75 80
Phe Arg Lys Phe Lys Leu Ile Thr Glu Asp Val Gln Gly Lys Asn Cys
85 90 95
Leu Thr Asn Phe His Gly Met Asp Leu Thr Arg Asp Lys Met Cys Ser
100 105 110
Met Val Lys Lys Trp Gln Thr Met Ile Glu Ala His Val Asp Val Lys
115 120 125
Thr Thr Asp Gly Tyr Leu Leu Arg Leu Phe Cys Val Gly Phe Thr Lys
130 135 140
Lys Arg Asn Asn Gln Ile Arg Lys Thr Ser Tyr Ala Gln His Gln Gln
145 150 155 160
Val Arg Gln Ile Arg Lys Lys Met Met Glu Ile Met Thr Arg Glu Val
165 170 175
Gln Thr Asn Asp Leu Lys Glu Val Val Asn Lys Leu Ile Pro Asp Ser
180 185 190
Ile Gly Lys Asp Ile Glu Lys Ala Cys Gln Ser Ile Tyr Pro Leu His
195 200 205
Asp Val Phe Val Arg Lys Val Lys Met Leu Lys Lys Pro Lys Phe Glu
210 215 220
Leu Gly Lys Leu Met Glu Leu His Gly Glu Gly Gly Ser Ser Gly Lys
225 230 235 240
Ala Ala Gly Asp Glu Thr Gly Ala Lys Val Glu Arg Ala Asp Gly Tyr
245 250 255
Glu Pro Pro Val Gln Glu Ser Val
260
Claims (4)
1.一种生物活性肽VSLADLQNDEVAFR，其特征在于，其氨基酸序列为Val-Ser-Leu-Ala-Asp-Leu-Gln-Asn-Asp-Glu-Val-Ala-Phe-Arg。
2.编码权利要求1所述生物活性肽VSLADLQNDEVAFR的多核苷酸。
3.如权利要求1所述生物活性肽VSLADLQNDEVAFR的制备方法，其特征在于，直接通过化学合成制备。
4.权利要求1所述生物活性肽VSLADLQNDEVAFR在制备具有免疫调节功能的药物中的应用，其特征在于，所述生物活性肽VSLADLQNDEVAFR促进体外巨噬细胞增殖。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011467487.6A CN112480232B (zh) | 2020-12-14 | 2020-12-14 | 一种生物活性肽vsladlqndevafr及其制备方法和应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011467487.6A CN112480232B (zh) | 2020-12-14 | 2020-12-14 | 一种生物活性肽vsladlqndevafr及其制备方法和应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112480232A CN112480232A (zh) | 2021-03-12 |
| CN112480232B true CN112480232B (zh) | 2022-07-15 |
Family
ID=74916951
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011467487.6A Active CN112480232B (zh) | 2020-12-14 | 2020-12-14 | 一种生物活性肽vsladlqndevafr及其制备方法和应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112480232B (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112592396B (zh) * | 2020-12-14 | 2022-10-21 | 上海交通大学 | 一种生物活性肽vdpfskkdw及其制备方法和应用 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1171133A (zh) * | 1994-10-14 | 1998-01-21 | 大制药株式会社 | 细胞凋亡相关基因 |
| CN101466737A (zh) * | 2006-04-10 | 2009-06-24 | 阿斯利康(瑞典)有限公司 | 针对uPAR的定向结合剂及其用途 |
| WO2015118184A1 (de) * | 2014-02-10 | 2015-08-13 | Protagen Ag | Markersequenzen zur diagnose und stratifizierung von sle patienten |
| CN107236031A (zh) * | 2017-07-06 | 2017-10-10 | 浙江辉肽生命健康科技有限公司 | 一种生物活性多肽pmigvnqelay及其制备方法和应用 |
| EP3424524A2 (en) * | 2017-07-04 | 2019-01-09 | CureVac AG | Cancer rna-vaccine |
| CN110938129A (zh) * | 2019-11-08 | 2020-03-31 | 上海交通大学 | 一种生物活性多肽sklvpvgygirkl及其制备方法和应用 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030165881A1 (en) * | 2000-03-07 | 2003-09-04 | Tang Y. Tom | Novel nucleic acids and polypeptides |
| CA2731216A1 (en) * | 2008-07-18 | 2010-01-21 | Oragenics, Inc. | Compositions for the detection and treatment of colorectal cancer |
-
2020
- 2020-12-14 CN CN202011467487.6A patent/CN112480232B/zh active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1171133A (zh) * | 1994-10-14 | 1998-01-21 | 大制药株式会社 | 细胞凋亡相关基因 |
| CN101466737A (zh) * | 2006-04-10 | 2009-06-24 | 阿斯利康(瑞典)有限公司 | 针对uPAR的定向结合剂及其用途 |
| WO2015118184A1 (de) * | 2014-02-10 | 2015-08-13 | Protagen Ag | Markersequenzen zur diagnose und stratifizierung von sle patienten |
| EP3424524A2 (en) * | 2017-07-04 | 2019-01-09 | CureVac AG | Cancer rna-vaccine |
| US10988754B2 (en) * | 2017-07-04 | 2021-04-27 | Cure Vac AG | Nucleic acid molecules |
| CN107236031A (zh) * | 2017-07-06 | 2017-10-10 | 浙江辉肽生命健康科技有限公司 | 一种生物活性多肽pmigvnqelay及其制备方法和应用 |
| CN110938129A (zh) * | 2019-11-08 | 2020-03-31 | 上海交通大学 | 一种生物活性多肽sklvpvgygirkl及其制备方法和应用 |
Non-Patent Citations (4)
| Title |
|---|
| hypothetical protein E5288_WYG009243 [Bos mutus];GenBank;《GenBank》;20200107;MXQ99474.1 * |
| retro_fcat_858，http://yeti.amu.edu.pl/retrogenedb/retrogene.php?RetroID=retro_fcat_858;RetrogeneDB;《RetrogeneDB》;20171231;retro_fcat_858 * |
| The in vivo effect of dimethyl sulphoxide (DMSO) on protein synthesis and the polyribosome profile in Paramecium;A H Reisner 等;《J Cell Physiol》;19770228;第90卷(第2期);第169-177页 * |
| 黄芩苷对T淋巴细胞增殖与活化的影响;梁清华 等;《全国第八届中西医结合风湿病学术会议论文汇编》;20101231;第306页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112480232A (zh) | 2021-03-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110938129B (zh) | 一种生物活性多肽sklvpvgygirkl及其制备方法和应用 | |
| CN112759636B (zh) | 具有氨基酸结构eslkgvdpkflr的生物活性肽及其制备方法和应用 | |
| CN112812168A (zh) | 一种生物活性肽glnmcrqcf及其制备方法和应用 | |
| CN112501140B (zh) | 一种生物活性多肽yfgsgfaapffivrhqllkk及其制备方法和应用 | |
| CN112625113B (zh) | 一种生物活性肽agydveknnsriklglk及其制备方法和应用 | |
| CN112480232B (zh) | 一种生物活性肽vsladlqndevafr及其制备方法和应用 | |
| CN112646022B (zh) | 一种生物活性肽pkcpkcdkevyfaerv及其制备方法和应用 | |
| CN112480233B (zh) | 一种生物活性肽iahpklgkrir及其制备方法和应用 | |
| CN112500468B (zh) | 一种生物活性肽rlafiahpklg及其制备方法和应用 | |
| CN112625112B (zh) | 一种生物活性多肽paapaqlpkki及其制备方法和应用 | |
| CN112500469B (zh) | 一种生物活性多肽aapaapaaappae及其制备方法和应用 | |
| CN112480234B (zh) | 一种生物活性肽aaggydveknnsriklglk及其制备方法和应用 | |
| CN112480231B (zh) | 一种生物活性肽kqslppglavkdlk及其制备方法和应用 | |
| CN112661830B (zh) | 具有氨基酸结构airndeelnkllgr的生物活性肽及其制备方法和应用 | |
| CN112574291B (zh) | 一种生物活性肽shrkfsaprhgslgflpr及其制备方法和应用 | |
| CN112481246B (zh) | 一种生物活性多肽fspankkltpkky及其制备方法和应用 | |
| CN112724237A (zh) | 一种生物活性肽ggsdgygsgrgf及其制备方法和应用 | |
| CN112745381B (zh) | 具有氨基酸结构nirnigktlvtr的生物活性肽及其制备方法和应用 | |
| CN112724239B (zh) | 具有氨基酸结构nkeldpvqklfvdkireyk的生物活性肽及其应用 | |
| CN112646023B (zh) | 具有氨基酸结构vnvvptfgkkkgp的生物活性肽及其制备方法和应用 | |
| CN112778410B (zh) | 一种生物活性肽saprhgslgflprk及其制备方法和应用 | |
| CN112759634B (zh) | 具有氨基酸结构feyieenky的生物活性肽及其制备方法和应用 | |
| CN112592902B (zh) | 一种生物活性肽aseppvldvkrpflc及其制备方法和应用 | |
| CN112480235B (zh) | 一种生物活性肽sgsaawddsaggaggqglrvtal及其制备方法和应用 | |
| CN112812169B (zh) | 具有氨基酸结构apkiqrlvtpr的生物活性肽及其制备方法和应用 |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |