CN114716538B - 一种人乳铁蛋白突变体及其与双歧杆菌在制备食品或保健品中的应用 - Google Patents
一种人乳铁蛋白突变体及其与双歧杆菌在制备食品或保健品中的应用 Download PDFInfo
- Publication number
- CN114716538B CN114716538B CN202210378074.3A CN202210378074A CN114716538B CN 114716538 B CN114716538 B CN 114716538B CN 202210378074 A CN202210378074 A CN 202210378074A CN 114716538 B CN114716538 B CN 114716538B
- Authority
- CN
- China
- Prior art keywords
- human lactoferrin
- mutant
- ala
- bifidobacteria
- leu
- 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
- 101000798114 Homo sapiens Lactotransferrin Proteins 0.000 title claims abstract description 58
- 102000050459 human LTF Human genes 0.000 title claims abstract description 58
- 241000186000 Bifidobacterium Species 0.000 title claims abstract description 31
- 235000013305 food Nutrition 0.000 title claims abstract description 16
- 230000036541 health Effects 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims description 9
- 239000000203 mixture Substances 0.000 claims abstract description 33
- 239000006041 probiotic Substances 0.000 claims abstract description 27
- 235000018291 probiotics Nutrition 0.000 claims abstract description 27
- 241001608472 Bifidobacterium longum Species 0.000 claims abstract description 15
- 229940009291 bifidobacterium longum Drugs 0.000 claims abstract description 15
- 241000894006 Bacteria Species 0.000 claims abstract description 13
- 241000186660 Lactobacillus Species 0.000 claims abstract description 9
- 108090000623 proteins and genes Proteins 0.000 claims description 24
- 239000013598 vector Substances 0.000 claims description 8
- 230000000529 probiotic effect Effects 0.000 claims description 6
- 241000588724 Escherichia coli Species 0.000 claims description 5
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000002773 nucleotide Substances 0.000 claims description 4
- 125000003729 nucleotide group Chemical group 0.000 claims description 4
- 241000186012 Bifidobacterium breve Species 0.000 claims description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 3
- 241000238631 Hexapoda Species 0.000 claims description 2
- 239000004310 lactic acid Substances 0.000 claims description 2
- 235000014655 lactic acid Nutrition 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 14
- 108060003951 Immunoglobulin Proteins 0.000 abstract description 13
- 102000018358 immunoglobulin Human genes 0.000 abstract description 13
- 229910052760 oxygen Inorganic materials 0.000 abstract description 13
- 239000001301 oxygen Substances 0.000 abstract description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 12
- 230000035755 proliferation Effects 0.000 abstract description 7
- 229940039696 lactobacillus Drugs 0.000 abstract description 6
- 241000194036 Lactococcus Species 0.000 abstract description 5
- 241000589517 Pseudomonas aeruginosa Species 0.000 abstract description 5
- 241000607142 Salmonella Species 0.000 abstract description 4
- 241000191967 Staphylococcus aureus Species 0.000 abstract description 4
- 230000006378 damage Effects 0.000 abstract description 4
- 230000005764 inhibitory process Effects 0.000 abstract description 3
- 230000036542 oxidative stress Effects 0.000 abstract description 3
- 208000027418 Wounds and injury Diseases 0.000 abstract description 2
- 230000001976 improved effect Effects 0.000 abstract description 2
- 208000014674 injury Diseases 0.000 abstract description 2
- 230000002829 reductive effect Effects 0.000 abstract description 2
- 102000010445 Lactoferrin Human genes 0.000 description 24
- 108010063045 Lactoferrin Proteins 0.000 description 24
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 22
- 235000021242 lactoferrin Nutrition 0.000 description 22
- 229940078795 lactoferrin Drugs 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 13
- 230000036039 immunity Effects 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 235000018102 proteins Nutrition 0.000 description 12
- 230000012010 growth Effects 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 8
- 229940099472 immunoglobulin a Drugs 0.000 description 7
- 229940027941 immunoglobulin g Drugs 0.000 description 7
- 230000001737 promoting effect Effects 0.000 description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- 210000001035 gastrointestinal tract Anatomy 0.000 description 6
- 150000001413 amino acids Chemical group 0.000 description 5
- 230000001580 bacterial effect Effects 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 244000005700 microbiome Species 0.000 description 5
- 108010047495 alanylglycine Proteins 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000036737 immune function Effects 0.000 description 4
- 229940072221 immunoglobulins Drugs 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 102000008133 Iron-Binding Proteins Human genes 0.000 description 3
- 108010035210 Iron-Binding Proteins Proteins 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 108010049041 glutamylalanine Proteins 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 235000020256 human milk Nutrition 0.000 description 3
- 210000004251 human milk Anatomy 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000035790 physiological processes and functions Effects 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 108010061238 threonyl-glycine Proteins 0.000 description 3
- 238000012795 verification Methods 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- NJPMYXWVWQWCSR-ACZMJKKPSA-N Ala-Glu-Asn Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NJPMYXWVWQWCSR-ACZMJKKPSA-N 0.000 description 2
- XACXDSRQIXRMNS-OLHMAJIHSA-N Asp-Asn-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)O)N)O XACXDSRQIXRMNS-OLHMAJIHSA-N 0.000 description 2
- YWLDTBBUHZJQHW-KKUMJFAQSA-N Asp-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)N YWLDTBBUHZJQHW-KKUMJFAQSA-N 0.000 description 2
- UQHYQYXOLIYNSR-CUJWVEQBSA-N Cys-His-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CS)N)O UQHYQYXOLIYNSR-CUJWVEQBSA-N 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- HXKZJLWGSWQKEA-LSJOCFKGSA-N His-Ala-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CN=CN1 HXKZJLWGSWQKEA-LSJOCFKGSA-N 0.000 description 2
- IBMVEYRWAWIOTN-UHFFFAOYSA-N L-Leucyl-L-Arginyl-L-Proline Natural products CC(C)CC(N)C(=O)NC(CCCN=C(N)N)C(=O)N1CCCC1C(O)=O IBMVEYRWAWIOTN-UHFFFAOYSA-N 0.000 description 2
- 241000880493 Leptailurus serval Species 0.000 description 2
- BIZNDKMFQHDOIE-KKUMJFAQSA-N Leu-Phe-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(O)=O)CC1=CC=CC=C1 BIZNDKMFQHDOIE-KKUMJFAQSA-N 0.000 description 2
- YSPZCHGIWAQVKQ-AVGNSLFASA-N Lys-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCCN YSPZCHGIWAQVKQ-AVGNSLFASA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- NVZVJIUDICCMHZ-BZSNNMDCSA-N Tyr-Phe-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O NVZVJIUDICCMHZ-BZSNNMDCSA-N 0.000 description 2
- DDRBQONWVBDQOY-GUBZILKMSA-N Val-Ala-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O DDRBQONWVBDQOY-GUBZILKMSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 235000020244 animal milk Nutrition 0.000 description 2
- 235000020247 cow milk Nutrition 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000001976 enzyme digestion Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 108010089804 glycyl-threonine Proteins 0.000 description 2
- 108010050848 glycylleucine Proteins 0.000 description 2
- 230000002519 immonomodulatory effect Effects 0.000 description 2
- 230000004957 immunoregulator effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 108010034529 leucyl-lysine Proteins 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 108010038320 lysylphenylalanine Proteins 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 238000012916 structural analysis Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- HPYLHFWTUAGUNX-BGZSDMPXSA-N (3s)-4-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-oxo-3-[[(2s,6s)-2,6,10-triamino-4-[(diaminomethylideneamino)methyl]-5-oxodecanoyl]amino]butanoic acid Chemical compound NCCCC[C@H](N)C(=O)C(CN=C(N)N)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O HPYLHFWTUAGUNX-BGZSDMPXSA-N 0.000 description 1
- ONEGZXHXCLCVRF-UHFFFAOYSA-N 2-[[2-[[1-(2-amino-3-methylbutanoyl)pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoic acid Chemical compound CC(C)CC(C(O)=O)NC(=O)C(C(C)C)NC(=O)C1CCCN1C(=O)C(N)C(C)C ONEGZXHXCLCVRF-UHFFFAOYSA-N 0.000 description 1
- GIPOFCXYHMWROH-UHFFFAOYSA-L 2-aminoacetate;iron(2+) Chemical compound [Fe+2].NCC([O-])=O.NCC([O-])=O GIPOFCXYHMWROH-UHFFFAOYSA-L 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
- IBSREHMXUMOFBB-JFUDTMANSA-N 5u8924t11h Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 IBSREHMXUMOFBB-JFUDTMANSA-N 0.000 description 1
- 239000005660 Abamectin Substances 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 241000186361 Actinobacteria <class> Species 0.000 description 1
- YLTKNGYYPIWKHZ-ACZMJKKPSA-N Ala-Ala-Glu Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O YLTKNGYYPIWKHZ-ACZMJKKPSA-N 0.000 description 1
- IMMKUCQIKKXKNP-DCAQKATOSA-N Ala-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CCCN=C(N)N IMMKUCQIKKXKNP-DCAQKATOSA-N 0.000 description 1
- NHCPCLJZRSIDHS-ZLUOBGJFSA-N Ala-Asp-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O NHCPCLJZRSIDHS-ZLUOBGJFSA-N 0.000 description 1
- WDIYWDJLXOCGRW-ACZMJKKPSA-N Ala-Asp-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WDIYWDJLXOCGRW-ACZMJKKPSA-N 0.000 description 1
- PCIFXPRIFWKWLK-YUMQZZPRSA-N Ala-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@H](C)N PCIFXPRIFWKWLK-YUMQZZPRSA-N 0.000 description 1
- BLIMFWGRQKRCGT-YUMQZZPRSA-N Ala-Gly-Lys Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCCN BLIMFWGRQKRCGT-YUMQZZPRSA-N 0.000 description 1
- DVJSJDDYCYSMFR-ZKWXMUAHSA-N Ala-Ile-Gly Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O DVJSJDDYCYSMFR-ZKWXMUAHSA-N 0.000 description 1
- WEZNQZHACPSMEF-QEJZJMRPSA-N Ala-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 WEZNQZHACPSMEF-QEJZJMRPSA-N 0.000 description 1
- YCRAFFCYWOUEOF-DLOVCJGASA-N Ala-Phe-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 YCRAFFCYWOUEOF-DLOVCJGASA-N 0.000 description 1
- IHMCQESUJVZTKW-UBHSHLNASA-N Ala-Phe-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CC1=CC=CC=C1 IHMCQESUJVZTKW-UBHSHLNASA-N 0.000 description 1
- VQAVBBCZFQAAED-FXQIFTODSA-N Ala-Pro-Asn Chemical compound C[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)N)C(=O)O)N VQAVBBCZFQAAED-FXQIFTODSA-N 0.000 description 1
- CQJHFKKGZXKZBC-BPNCWPANSA-N Ala-Pro-Tyr Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CQJHFKKGZXKZBC-BPNCWPANSA-N 0.000 description 1
- WQKAQKZRDIZYNV-VZFHVOOUSA-N Ala-Ser-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WQKAQKZRDIZYNV-VZFHVOOUSA-N 0.000 description 1
- SAHQGRZIQVEJPF-JXUBOQSCSA-N Ala-Thr-Lys Chemical compound C[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCCN SAHQGRZIQVEJPF-JXUBOQSCSA-N 0.000 description 1
- VHAQSYHSDKERBS-XPUUQOCRSA-N Ala-Val-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O VHAQSYHSDKERBS-XPUUQOCRSA-N 0.000 description 1
- IGULQRCJLQQPSM-DCAQKATOSA-N Arg-Cys-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(O)=O IGULQRCJLQQPSM-DCAQKATOSA-N 0.000 description 1
- FEZJJKXNPSEYEV-CIUDSAMLSA-N Arg-Gln-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O FEZJJKXNPSEYEV-CIUDSAMLSA-N 0.000 description 1
- WVNFNPGXYADPPO-BQBZGAKWSA-N Arg-Gly-Ser Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O WVNFNPGXYADPPO-BQBZGAKWSA-N 0.000 description 1
- YKBHOXLMMPZPHQ-GMOBBJLQSA-N Arg-Ile-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O YKBHOXLMMPZPHQ-GMOBBJLQSA-N 0.000 description 1
- ADPACBMPYWJJCE-FXQIFTODSA-N Arg-Ser-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O ADPACBMPYWJJCE-FXQIFTODSA-N 0.000 description 1
- AUIJUTGLPVHIRT-FXQIFTODSA-N Arg-Ser-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N)CN=C(N)N AUIJUTGLPVHIRT-FXQIFTODSA-N 0.000 description 1
- ASQKVGRCKOFKIU-KZVJFYERSA-N Arg-Thr-Ala Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O ASQKVGRCKOFKIU-KZVJFYERSA-N 0.000 description 1
- SUMJNGAMIQSNGX-TUAOUCFPSA-N Arg-Val-Pro Chemical compound CC(C)[C@H](NC(=O)[C@@H](N)CCCNC(N)=N)C(=O)N1CCC[C@@H]1C(O)=O SUMJNGAMIQSNGX-TUAOUCFPSA-N 0.000 description 1
- FTCGGKNCJZOPNB-WHFBIAKZSA-N Asn-Gly-Ser Chemical compound NC(=O)C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O FTCGGKNCJZOPNB-WHFBIAKZSA-N 0.000 description 1
- GLWFAWNYGWBMOC-SRVKXCTJSA-N Asn-Leu-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O GLWFAWNYGWBMOC-SRVKXCTJSA-N 0.000 description 1
- FODVBOKTYKYRFJ-CIUDSAMLSA-N Asn-Lys-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N FODVBOKTYKYRFJ-CIUDSAMLSA-N 0.000 description 1
- ICDDSTLEMLGSTB-GUBZILKMSA-N Asn-Met-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ICDDSTLEMLGSTB-GUBZILKMSA-N 0.000 description 1
- REQUGIWGOGSOEZ-ZLUOBGJFSA-N Asn-Ser-Asn Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)O)N)C(=O)N REQUGIWGOGSOEZ-ZLUOBGJFSA-N 0.000 description 1
- ULZOQOKFYMXHPZ-AQZXSJQPSA-N Asn-Trp-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ULZOQOKFYMXHPZ-AQZXSJQPSA-N 0.000 description 1
- XBQSLMACWDXWLJ-GHCJXIJMSA-N Asp-Ala-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O XBQSLMACWDXWLJ-GHCJXIJMSA-N 0.000 description 1
- KVPHTGVUMJGMCX-BIIVOSGPSA-N Asp-Cys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CS)NC(=O)[C@H](CC(=O)O)N)C(=O)O KVPHTGVUMJGMCX-BIIVOSGPSA-N 0.000 description 1
- DTNUIAJCPRMNBT-WHFBIAKZSA-N Asp-Gly-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(O)=O DTNUIAJCPRMNBT-WHFBIAKZSA-N 0.000 description 1
- JUWZKMBALYLZCK-WHFBIAKZSA-N Asp-Gly-Asn Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O JUWZKMBALYLZCK-WHFBIAKZSA-N 0.000 description 1
- OMMIEVATLAGRCK-BYPYZUCNSA-N Asp-Gly-Gly Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)NCC(O)=O OMMIEVATLAGRCK-BYPYZUCNSA-N 0.000 description 1
- UJGRZQYSNYTCAX-SRVKXCTJSA-N Asp-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(O)=O UJGRZQYSNYTCAX-SRVKXCTJSA-N 0.000 description 1
- DPNWSMBUYCLEDG-CIUDSAMLSA-N Asp-Lys-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O DPNWSMBUYCLEDG-CIUDSAMLSA-N 0.000 description 1
- ZKAOJVJQGVUIIU-GUBZILKMSA-N Asp-Pro-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ZKAOJVJQGVUIIU-GUBZILKMSA-N 0.000 description 1
- BWJZSLQJNBSUPM-FXQIFTODSA-N Asp-Pro-Asn Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O BWJZSLQJNBSUPM-FXQIFTODSA-N 0.000 description 1
- 241000186016 Bifidobacterium bifidum Species 0.000 description 1
- 241000193171 Clostridium butyricum Species 0.000 description 1
- 241000193468 Clostridium perfringens Species 0.000 description 1
- AEJSNWMRPXAKCW-WHFBIAKZSA-N Cys-Ala-Gly Chemical compound SC[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O AEJSNWMRPXAKCW-WHFBIAKZSA-N 0.000 description 1
- NOCCABSVTRONIN-CIUDSAMLSA-N Cys-Ala-Leu Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CS)N NOCCABSVTRONIN-CIUDSAMLSA-N 0.000 description 1
- YFXFOZPXVFPBDH-VZFHVOOUSA-N Cys-Ala-Thr Chemical compound C[C@@H](O)[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)CS)C(O)=O YFXFOZPXVFPBDH-VZFHVOOUSA-N 0.000 description 1
- UISYPAHPLXGLNH-ACZMJKKPSA-N Cys-Asn-Gln Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O UISYPAHPLXGLNH-ACZMJKKPSA-N 0.000 description 1
- LBOLGUYQEPZSKM-YUMQZZPRSA-N Cys-Gly-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CS)N LBOLGUYQEPZSKM-YUMQZZPRSA-N 0.000 description 1
- ZMWOJVAXTOUHAP-ZKWXMUAHSA-N Cys-Ile-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CS)N ZMWOJVAXTOUHAP-ZKWXMUAHSA-N 0.000 description 1
- KXUKWRVYDYIPSQ-CIUDSAMLSA-N Cys-Leu-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O KXUKWRVYDYIPSQ-CIUDSAMLSA-N 0.000 description 1
- ABLJDBFJPUWQQB-DCAQKATOSA-N Cys-Leu-Arg Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CS)N ABLJDBFJPUWQQB-DCAQKATOSA-N 0.000 description 1
- BLGNLNRBABWDST-CIUDSAMLSA-N Cys-Leu-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CS)N BLGNLNRBABWDST-CIUDSAMLSA-N 0.000 description 1
- KCPOQGRVVXYLAC-KKUMJFAQSA-N Cys-Leu-Phe Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CS)N KCPOQGRVVXYLAC-KKUMJFAQSA-N 0.000 description 1
- BBQIWFFTTQTNOC-AVGNSLFASA-N Cys-Phe-Gln Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CS)N BBQIWFFTTQTNOC-AVGNSLFASA-N 0.000 description 1
- YNJBLTDKTMKEET-ZLUOBGJFSA-N Cys-Ser-Ser Chemical compound SC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O YNJBLTDKTMKEET-ZLUOBGJFSA-N 0.000 description 1
- DQGIAOGALAQBGK-BWBBJGPYSA-N Cys-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CS)N)O DQGIAOGALAQBGK-BWBBJGPYSA-N 0.000 description 1
- DGQJGBDBFVGLGL-ZKWXMUAHSA-N Cys-Val-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CS)N DGQJGBDBFVGLGL-ZKWXMUAHSA-N 0.000 description 1
- QQAYIVHVRFJICE-AEJSXWLSSA-N Cys-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CS)N QQAYIVHVRFJICE-AEJSXWLSSA-N 0.000 description 1
- 235000011201 Ginkgo Nutrition 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- 235000008100 Ginkgo biloba Nutrition 0.000 description 1
- AAOBFSKXAVIORT-GUBZILKMSA-N Gln-Asn-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O AAOBFSKXAVIORT-GUBZILKMSA-N 0.000 description 1
- GMGKDVVBSVVKCT-NUMRIWBASA-N Gln-Asn-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GMGKDVVBSVVKCT-NUMRIWBASA-N 0.000 description 1
- LPYPANUXJGFMGV-FXQIFTODSA-N Gln-Gln-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N LPYPANUXJGFMGV-FXQIFTODSA-N 0.000 description 1
- RBWKVOSARCFSQQ-FXQIFTODSA-N Gln-Gln-Ser Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O RBWKVOSARCFSQQ-FXQIFTODSA-N 0.000 description 1
- PNENQZWRFMUZOM-DCAQKATOSA-N Gln-Glu-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O PNENQZWRFMUZOM-DCAQKATOSA-N 0.000 description 1
- MAGNEQBFSBREJL-DCAQKATOSA-N Gln-Glu-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)N MAGNEQBFSBREJL-DCAQKATOSA-N 0.000 description 1
- XUMFMAVDHQDATI-DCAQKATOSA-N Gln-Pro-Arg Chemical compound NC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O XUMFMAVDHQDATI-DCAQKATOSA-N 0.000 description 1
- HMIXCETWRYDVMO-GUBZILKMSA-N Gln-Pro-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O HMIXCETWRYDVMO-GUBZILKMSA-N 0.000 description 1
- MFHVAWMMKZBSRQ-ACZMJKKPSA-N Gln-Ser-Cys Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N MFHVAWMMKZBSRQ-ACZMJKKPSA-N 0.000 description 1
- RWQCWSGOOOEGPB-FXQIFTODSA-N Gln-Ser-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(O)=O RWQCWSGOOOEGPB-FXQIFTODSA-N 0.000 description 1
- ININBLZFFVOQIO-JHEQGTHGSA-N Gln-Thr-Gly Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CCC(=O)N)N)O ININBLZFFVOQIO-JHEQGTHGSA-N 0.000 description 1
- LKDIBBOKUAASNP-FXQIFTODSA-N Glu-Ala-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LKDIBBOKUAASNP-FXQIFTODSA-N 0.000 description 1
- KKCUFHUTMKQQCF-SRVKXCTJSA-N Glu-Arg-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O KKCUFHUTMKQQCF-SRVKXCTJSA-N 0.000 description 1
- RQNYYRHRKSVKAB-GUBZILKMSA-N Glu-Cys-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(O)=O RQNYYRHRKSVKAB-GUBZILKMSA-N 0.000 description 1
- XHUCVVHRLNPZSZ-CIUDSAMLSA-N Glu-Gln-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O XHUCVVHRLNPZSZ-CIUDSAMLSA-N 0.000 description 1
- WXONSNSSBYQGNN-AVGNSLFASA-N Glu-Ser-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O WXONSNSSBYQGNN-AVGNSLFASA-N 0.000 description 1
- GPSHCSTUYOQPAI-JHEQGTHGSA-N Glu-Thr-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O GPSHCSTUYOQPAI-JHEQGTHGSA-N 0.000 description 1
- BKMOHWJHXQLFEX-IRIUXVKKSA-N Glu-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CCC(=O)O)N)O BKMOHWJHXQLFEX-IRIUXVKKSA-N 0.000 description 1
- RLFSBAPJTYKSLG-WHFBIAKZSA-N Gly-Ala-Asp Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(O)=O RLFSBAPJTYKSLG-WHFBIAKZSA-N 0.000 description 1
- MZZSCEANQDPJER-ONGXEEELSA-N Gly-Ala-Phe Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MZZSCEANQDPJER-ONGXEEELSA-N 0.000 description 1
- UPOJUWHGMDJUQZ-IUCAKERBSA-N Gly-Arg-Arg Chemical compound NC(=N)NCCC[C@H](NC(=O)CN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O UPOJUWHGMDJUQZ-IUCAKERBSA-N 0.000 description 1
- AQLHORCVPGXDJW-IUCAKERBSA-N Gly-Gln-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)CN AQLHORCVPGXDJW-IUCAKERBSA-N 0.000 description 1
- KAJAOGBVWCYGHZ-JTQLQIEISA-N Gly-Gly-Phe Chemical compound [NH3+]CC(=O)NCC(=O)N[C@H](C([O-])=O)CC1=CC=CC=C1 KAJAOGBVWCYGHZ-JTQLQIEISA-N 0.000 description 1
- NSTUFLGQJCOCDL-UWVGGRQHSA-N Gly-Leu-Arg Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N NSTUFLGQJCOCDL-UWVGGRQHSA-N 0.000 description 1
- AFWYPMDMDYCKMD-KBPBESRZSA-N Gly-Leu-Tyr Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 AFWYPMDMDYCKMD-KBPBESRZSA-N 0.000 description 1
- CLNSYANKYVMZNM-UWVGGRQHSA-N Gly-Lys-Arg Chemical compound NCCCC[C@H](NC(=O)CN)C(=O)N[C@H](C(O)=O)CCCN=C(N)N CLNSYANKYVMZNM-UWVGGRQHSA-N 0.000 description 1
- GMTXWRIDLGTVFC-IUCAKERBSA-N Gly-Lys-Glu Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O GMTXWRIDLGTVFC-IUCAKERBSA-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
- HJARVELKOSZUEW-YUMQZZPRSA-N Gly-Pro-Gln Chemical compound [H]NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O HJARVELKOSZUEW-YUMQZZPRSA-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
- OCRQUYDOYKCOQG-IRXDYDNUSA-N Gly-Tyr-Phe Chemical compound C([C@H](NC(=O)CN)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 OCRQUYDOYKCOQG-IRXDYDNUSA-N 0.000 description 1
- RVKIPWVMZANZLI-UHFFFAOYSA-N H-Lys-Trp-OH Natural products C1=CC=C2C(CC(NC(=O)C(N)CCCCN)C(O)=O)=CNC2=C1 RVKIPWVMZANZLI-UHFFFAOYSA-N 0.000 description 1
- VYUXYMRNGALHEA-DLOVCJGASA-N His-Leu-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O VYUXYMRNGALHEA-DLOVCJGASA-N 0.000 description 1
- VAXBXNPRXPHGHG-BJDJZHNGSA-N Ile-Ala-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)O)N VAXBXNPRXPHGHG-BJDJZHNGSA-N 0.000 description 1
- SAEWJTCJQVZQNZ-IUKAMOBKSA-N Ile-Thr-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N SAEWJTCJQVZQNZ-IUKAMOBKSA-N 0.000 description 1
- RMJWFINHACYKJI-SIUGBPQLSA-N Ile-Tyr-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N RMJWFINHACYKJI-SIUGBPQLSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000015710 Iron-Deficiency Anemia Diseases 0.000 description 1
- 108010079091 KRDS peptide Proteins 0.000 description 1
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 description 1
- FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 description 1
- SITWEMZOJNKJCH-UHFFFAOYSA-N L-alanine-L-arginine Natural products CC(N)C(=O)NC(C(O)=O)CCCNC(N)=N SITWEMZOJNKJCH-UHFFFAOYSA-N 0.000 description 1
- SENJXOPIZNYLHU-UHFFFAOYSA-N L-leucyl-L-arginine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CCCN=C(N)N SENJXOPIZNYLHU-UHFFFAOYSA-N 0.000 description 1
- IJKRDVKGCQRKBI-UHFFFAOYSA-N Lactobacillinsaeure Natural products CCCCCCC1CC1CCCCCCCCCC(O)=O IJKRDVKGCQRKBI-UHFFFAOYSA-N 0.000 description 1
- DQPQTXMIRBUWKO-DCAQKATOSA-N Leu-Ala-Met Chemical compound C[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CC(C)C)N DQPQTXMIRBUWKO-DCAQKATOSA-N 0.000 description 1
- YOZCKMXHBYKOMQ-IHRRRGAJSA-N Leu-Arg-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O)N YOZCKMXHBYKOMQ-IHRRRGAJSA-N 0.000 description 1
- KKXDHFKZWKLYGB-GUBZILKMSA-N Leu-Asn-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N KKXDHFKZWKLYGB-GUBZILKMSA-N 0.000 description 1
- NFHJQETXTSDZSI-DCAQKATOSA-N Leu-Cys-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O NFHJQETXTSDZSI-DCAQKATOSA-N 0.000 description 1
- HUEBCHPSXSQUGN-GARJFASQSA-N Leu-Cys-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)N1CCC[C@@H]1C(=O)O)N HUEBCHPSXSQUGN-GARJFASQSA-N 0.000 description 1
- DPWGZWUMUUJQDT-IUCAKERBSA-N Leu-Gln-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O DPWGZWUMUUJQDT-IUCAKERBSA-N 0.000 description 1
- DZQMXBALGUHGJT-GUBZILKMSA-N Leu-Glu-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O DZQMXBALGUHGJT-GUBZILKMSA-N 0.000 description 1
- VGPCJSXPPOQPBK-YUMQZZPRSA-N Leu-Gly-Ser Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O VGPCJSXPPOQPBK-YUMQZZPRSA-N 0.000 description 1
- KYIIALJHAOIAHF-KKUMJFAQSA-N Leu-Leu-His Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 KYIIALJHAOIAHF-KKUMJFAQSA-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
- VCHVSKNMTXWIIP-SRVKXCTJSA-N Leu-Lys-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O VCHVSKNMTXWIIP-SRVKXCTJSA-N 0.000 description 1
- INCJJHQRZGQLFC-KBPBESRZSA-N Leu-Phe-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(O)=O INCJJHQRZGQLFC-KBPBESRZSA-N 0.000 description 1
- 206010024642 Listless Diseases 0.000 description 1
- FACUGMGEFUEBTI-SRVKXCTJSA-N Lys-Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CCCCN FACUGMGEFUEBTI-SRVKXCTJSA-N 0.000 description 1
- SQXUUGUCGJSWCK-CIUDSAMLSA-N Lys-Asp-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N SQXUUGUCGJSWCK-CIUDSAMLSA-N 0.000 description 1
- NRQRKMYZONPCTM-CIUDSAMLSA-N Lys-Asp-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O NRQRKMYZONPCTM-CIUDSAMLSA-N 0.000 description 1
- GKFNXYMAMKJSKD-NHCYSSNCSA-N Lys-Asp-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O GKFNXYMAMKJSKD-NHCYSSNCSA-N 0.000 description 1
- NDORZBUHCOJQDO-GVXVVHGQSA-N Lys-Gln-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O NDORZBUHCOJQDO-GVXVVHGQSA-N 0.000 description 1
- XNKDCYABMBBEKN-IUCAKERBSA-N Lys-Gly-Gln Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O XNKDCYABMBBEKN-IUCAKERBSA-N 0.000 description 1
- LCMWVZLBCUVDAZ-IUCAKERBSA-N Lys-Gly-Glu Chemical compound [NH3+]CCCC[C@H]([NH3+])C(=O)NCC(=O)N[C@H](C([O-])=O)CCC([O-])=O LCMWVZLBCUVDAZ-IUCAKERBSA-N 0.000 description 1
- ISHNZELVUVPCHY-ZETCQYMHSA-N Lys-Gly-Gly Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)NCC(O)=O ISHNZELVUVPCHY-ZETCQYMHSA-N 0.000 description 1
- OVAOHZIOUBEQCJ-IHRRRGAJSA-N Lys-Leu-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O OVAOHZIOUBEQCJ-IHRRRGAJSA-N 0.000 description 1
- YDDDRTIPNTWGIG-SRVKXCTJSA-N Lys-Lys-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O YDDDRTIPNTWGIG-SRVKXCTJSA-N 0.000 description 1
- PIXVFCBYEGPZPA-JYJNAYRXSA-N Lys-Phe-Gln Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N PIXVFCBYEGPZPA-JYJNAYRXSA-N 0.000 description 1
- MSSJJDVQTFTLIF-KBPBESRZSA-N Lys-Phe-Gly Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(O)=O MSSJJDVQTFTLIF-KBPBESRZSA-N 0.000 description 1
- MIMXMVDLMDMOJD-BZSNNMDCSA-N Lys-Tyr-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O MIMXMVDLMDMOJD-BZSNNMDCSA-N 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- DRXODWRPPUFIAY-DCAQKATOSA-N Met-Asn-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CCCCN DRXODWRPPUFIAY-DCAQKATOSA-N 0.000 description 1
- WGBMNLCRYKSWAR-DCAQKATOSA-N Met-Asp-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN WGBMNLCRYKSWAR-DCAQKATOSA-N 0.000 description 1
- HLZORBMOISUNIV-DCAQKATOSA-N Met-Ser-Leu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(C)C HLZORBMOISUNIV-DCAQKATOSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 108010021466 Mutant Proteins Proteins 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
- AJHCSUXXECOXOY-UHFFFAOYSA-N N-glycyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)CN)C(O)=O)=CNC2=C1 AJHCSUXXECOXOY-UHFFFAOYSA-N 0.000 description 1
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 1
- 108010087066 N2-tryptophyllysine Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- DDYIRGBOZVKRFR-AVGNSLFASA-N Phe-Asp-Glu Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N DDYIRGBOZVKRFR-AVGNSLFASA-N 0.000 description 1
- HBGFEEQFVBWYJQ-KBPBESRZSA-N Phe-Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CC=CC=C1 HBGFEEQFVBWYJQ-KBPBESRZSA-N 0.000 description 1
- GPLWGAYGROGDEN-BZSNNMDCSA-N Phe-Phe-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O GPLWGAYGROGDEN-BZSNNMDCSA-N 0.000 description 1
- RVEVENLSADZUMS-IHRRRGAJSA-N Phe-Pro-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O RVEVENLSADZUMS-IHRRRGAJSA-N 0.000 description 1
- DXTOOBDIIAJZBJ-BQBZGAKWSA-N Pro-Gly-Ser Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CO)C(O)=O DXTOOBDIIAJZBJ-BQBZGAKWSA-N 0.000 description 1
- BWCZJGJKOFUUCN-ZPFDUUQYSA-N Pro-Ile-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O BWCZJGJKOFUUCN-ZPFDUUQYSA-N 0.000 description 1
- KWMUAKQOVYCQJQ-ZPFDUUQYSA-N Pro-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]1CCCN1 KWMUAKQOVYCQJQ-ZPFDUUQYSA-N 0.000 description 1
- XYHMFGGWNOFUOU-QXEWZRGKSA-N Pro-Ile-Gly Chemical compound OC(=O)CNC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]1CCCN1 XYHMFGGWNOFUOU-QXEWZRGKSA-N 0.000 description 1
- WIPAMEKBSHNFQE-IUCAKERBSA-N Pro-Met-Gly Chemical compound CSCC[C@@H](C(=O)NCC(=O)O)NC(=O)[C@@H]1CCCN1 WIPAMEKBSHNFQE-IUCAKERBSA-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
- KBUAPZAZPWNYSW-SRVKXCTJSA-N Pro-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 KBUAPZAZPWNYSW-SRVKXCTJSA-N 0.000 description 1
- IMNVAOPEMFDAQD-NHCYSSNCSA-N Pro-Val-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O IMNVAOPEMFDAQD-NHCYSSNCSA-N 0.000 description 1
- 238000012356 Product development Methods 0.000 description 1
- 241000233671 Schizochytrium Species 0.000 description 1
- FIDMVVBUOCMMJG-CIUDSAMLSA-N Ser-Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CO FIDMVVBUOCMMJG-CIUDSAMLSA-N 0.000 description 1
- GHPQVUYZQQGEDA-BIIVOSGPSA-N Ser-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)N)C(=O)O GHPQVUYZQQGEDA-BIIVOSGPSA-N 0.000 description 1
- INCNPLPRPOYTJI-JBDRJPRFSA-N Ser-Cys-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CO)N INCNPLPRPOYTJI-JBDRJPRFSA-N 0.000 description 1
- KMWFXJCGRXBQAC-CIUDSAMLSA-N Ser-Cys-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CO)N KMWFXJCGRXBQAC-CIUDSAMLSA-N 0.000 description 1
- ZOHGLPQGEHSLPD-FXQIFTODSA-N Ser-Gln-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZOHGLPQGEHSLPD-FXQIFTODSA-N 0.000 description 1
- YRBGKVIWMNEVCZ-WDSKDSINSA-N Ser-Glu-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O YRBGKVIWMNEVCZ-WDSKDSINSA-N 0.000 description 1
- MUJQWSAWLLRJCE-KATARQTJSA-N Ser-Leu-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MUJQWSAWLLRJCE-KATARQTJSA-N 0.000 description 1
- FZEUTKVQGMVGHW-AVGNSLFASA-N Ser-Phe-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O FZEUTKVQGMVGHW-AVGNSLFASA-N 0.000 description 1
- FKYWFUYPVKLJLP-DCAQKATOSA-N Ser-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO FKYWFUYPVKLJLP-DCAQKATOSA-N 0.000 description 1
- AZWNCEBQZXELEZ-FXQIFTODSA-N Ser-Pro-Ser Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O AZWNCEBQZXELEZ-FXQIFTODSA-N 0.000 description 1
- KQNDIKOYWZTZIX-FXQIFTODSA-N Ser-Ser-Arg Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCNC(N)=N KQNDIKOYWZTZIX-FXQIFTODSA-N 0.000 description 1
- PCMZJFMUYWIERL-ZKWXMUAHSA-N Ser-Val-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O PCMZJFMUYWIERL-ZKWXMUAHSA-N 0.000 description 1
- SIEBDTCABMZCLF-XGEHTFHBSA-N Ser-Val-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SIEBDTCABMZCLF-XGEHTFHBSA-N 0.000 description 1
- 241001052560 Thallis Species 0.000 description 1
- TYVAWPFQYFPSBR-BFHQHQDPSA-N Thr-Ala-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)NCC(O)=O TYVAWPFQYFPSBR-BFHQHQDPSA-N 0.000 description 1
- PXQUBKWZENPDGE-CIQUZCHMSA-N Thr-Ala-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)O)N PXQUBKWZENPDGE-CIQUZCHMSA-N 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
- FHDLKMFZKRUQCE-HJGDQZAQSA-N Thr-Glu-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FHDLKMFZKRUQCE-HJGDQZAQSA-N 0.000 description 1
- LGNBRHZANHMZHK-NUMRIWBASA-N Thr-Glu-Asp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)O LGNBRHZANHMZHK-NUMRIWBASA-N 0.000 description 1
- AQAMPXBRJJWPNI-JHEQGTHGSA-N Thr-Gly-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O AQAMPXBRJJWPNI-JHEQGTHGSA-N 0.000 description 1
- YDWLCDQXLCILCZ-BWAGICSOSA-N Thr-His-Tyr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O YDWLCDQXLCILCZ-BWAGICSOSA-N 0.000 description 1
- AMXMBCAXAZUCFA-RHYQMDGZSA-N Thr-Leu-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AMXMBCAXAZUCFA-RHYQMDGZSA-N 0.000 description 1
- REJRKTOJTCPDPO-IRIUXVKKSA-N Thr-Tyr-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O REJRKTOJTCPDPO-IRIUXVKKSA-N 0.000 description 1
- BKVICMPZWRNWOC-RHYQMDGZSA-N Thr-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)[C@@H](C)O BKVICMPZWRNWOC-RHYQMDGZSA-N 0.000 description 1
- LAIUAVGWZYTBKN-VHWLVUOQSA-N Trp-Asn-Ile Chemical compound CC[C@H](C)[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)Cc1c[nH]c2ccccc12)C(O)=O LAIUAVGWZYTBKN-VHWLVUOQSA-N 0.000 description 1
- UKINEYBQXPMOJO-UBHSHLNASA-N Trp-Asn-Ser Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CO)C(=O)O)N UKINEYBQXPMOJO-UBHSHLNASA-N 0.000 description 1
- XZSJDSBPEJBEFZ-QRTARXTBSA-N Trp-Asn-Val Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O XZSJDSBPEJBEFZ-QRTARXTBSA-N 0.000 description 1
- XZLHHHYSWIYXHD-XIRDDKMYSA-N Trp-Gln-Arg Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O XZLHHHYSWIYXHD-XIRDDKMYSA-N 0.000 description 1
- UJGDFQRPYGJBEH-AAEUAGOBSA-N Trp-Ser-Gly Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CO)C(=O)NCC(=O)O)N UJGDFQRPYGJBEH-AAEUAGOBSA-N 0.000 description 1
- PALLCTDPFINNMM-JQHSSLGASA-N Trp-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N PALLCTDPFINNMM-JQHSSLGASA-N 0.000 description 1
- DXYWRYQRKPIGGU-BPNCWPANSA-N Tyr-Ala-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 DXYWRYQRKPIGGU-BPNCWPANSA-N 0.000 description 1
- PGEFRHBWGOJPJT-KKUMJFAQSA-N Tyr-Lys-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O PGEFRHBWGOJPJT-KKUMJFAQSA-N 0.000 description 1
- ZPFLBLFITJCBTP-QWRGUYRKSA-N Tyr-Ser-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)NCC(O)=O ZPFLBLFITJCBTP-QWRGUYRKSA-N 0.000 description 1
- RGJZPXFZIUUQDN-BPNCWPANSA-N Tyr-Val-Ala Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O RGJZPXFZIUUQDN-BPNCWPANSA-N 0.000 description 1
- COYSIHFOCOMGCF-WPRPVWTQSA-N Val-Arg-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CCCN=C(N)N COYSIHFOCOMGCF-WPRPVWTQSA-N 0.000 description 1
- COYSIHFOCOMGCF-UHFFFAOYSA-N Val-Arg-Gly Natural products CC(C)C(N)C(=O)NC(C(=O)NCC(O)=O)CCCN=C(N)N COYSIHFOCOMGCF-UHFFFAOYSA-N 0.000 description 1
- XQVRMLRMTAGSFJ-QXEWZRGKSA-N Val-Asp-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N XQVRMLRMTAGSFJ-QXEWZRGKSA-N 0.000 description 1
- XXWBHOWRARMUOC-NHCYSSNCSA-N Val-Lys-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N)C(=O)O)N XXWBHOWRARMUOC-NHCYSSNCSA-N 0.000 description 1
- DIOSYUIWOQCXNR-ONGXEEELSA-N Val-Lys-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O DIOSYUIWOQCXNR-ONGXEEELSA-N 0.000 description 1
- DOFAQXCYFQKSHT-SRVKXCTJSA-N Val-Pro-Pro Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DOFAQXCYFQKSHT-SRVKXCTJSA-N 0.000 description 1
- AJNUKMZFHXUBMK-GUBZILKMSA-N Val-Ser-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N AJNUKMZFHXUBMK-GUBZILKMSA-N 0.000 description 1
- GUIYPEKUEMQBIK-JSGCOSHPSA-N Val-Tyr-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)NCC(O)=O GUIYPEKUEMQBIK-JSGCOSHPSA-N 0.000 description 1
- BGTDGENDNWGMDQ-KJEVXHAQSA-N Val-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](C(C)C)N)O BGTDGENDNWGMDQ-KJEVXHAQSA-N 0.000 description 1
- RTJPAGFXOWEBAI-SRVKXCTJSA-N Val-Val-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N RTJPAGFXOWEBAI-SRVKXCTJSA-N 0.000 description 1
- AOILQMZPNLUXCM-AVGNSLFASA-N Val-Val-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN AOILQMZPNLUXCM-AVGNSLFASA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 229950008167 abamectin Drugs 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 108010039538 alanyl-glycyl-aspartyl-valine Proteins 0.000 description 1
- 108010045023 alanyl-prolyl-tyrosine Proteins 0.000 description 1
- 108010044940 alanylglutamine Proteins 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 108010008355 arginyl-glutamine Proteins 0.000 description 1
- 108010091092 arginyl-glycyl-proline Proteins 0.000 description 1
- 108010069926 arginyl-glycyl-serine Proteins 0.000 description 1
- 108010068380 arginylarginine Proteins 0.000 description 1
- 108010062796 arginyllysine Proteins 0.000 description 1
- 108010047857 aspartylglycine Proteins 0.000 description 1
- 108010092854 aspartyllysine Proteins 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 108010080575 glutamyl-aspartyl-alanine Proteins 0.000 description 1
- 102000035122 glycosylated proteins Human genes 0.000 description 1
- 108091005608 glycosylated proteins Proteins 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
- 108010075431 glycyl-alanyl-phenylalanine Proteins 0.000 description 1
- 108010050475 glycyl-leucyl-tyrosine Proteins 0.000 description 1
- 108010074027 glycyl-seryl-phenylalanine Proteins 0.000 description 1
- 108010015792 glycyllysine Proteins 0.000 description 1
- 108010087823 glycyltyrosine Proteins 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 150000003278 haem Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000008975 immunomodulatory function Effects 0.000 description 1
- 208000033065 inborn errors of immunity Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- IJKRDVKGCQRKBI-ZWKOTPCHSA-N lactobacillic acid Chemical compound CCCCCC[C@H]1C[C@H]1CCCCCCCCCC(O)=O IJKRDVKGCQRKBI-ZWKOTPCHSA-N 0.000 description 1
- 108010000761 leucylarginine Proteins 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 208000017971 listlessness Diseases 0.000 description 1
- 108010003700 lysyl aspartic acid Proteins 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000004060 metabolic process Effects 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
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 230000003472 neutralizing effect Effects 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
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000002926 oxygen Chemical class 0.000 description 1
- -1 oxygen free radical Chemical class 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 108010018625 phenylalanylarginine Proteins 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 208000028529 primary immunodeficiency disease Diseases 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108010031719 prolyl-serine Proteins 0.000 description 1
- 108010029020 prolylglycine Proteins 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000035806 respiratory chain Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 108010026333 seryl-proline Proteins 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 208000020685 sleep-wake disease Diseases 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 210000001138 tear Anatomy 0.000 description 1
- 229940015977 teferrol Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 108010003137 tyrosyltyrosine Proteins 0.000 description 1
- 210000002229 urogenital system Anatomy 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 108010015385 valyl-prolyl-proline Proteins 0.000 description 1
- 108010073969 valyllysine Proteins 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 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
- C07K14/79—Transferrins, e.g. lactoferrins, ovotransferrins
-
- 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
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
-
- 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
- A23L33/19—Dairy proteins
-
- 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
- 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
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/51—Bifidobacterium
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Toxicology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
本发明涉及一种人乳铁蛋白突变体及其与双歧杆菌在制备食品或保健品中的应用。具体涉及一种人乳铁蛋白突变体,能够显著促进双歧杆菌、乳杆菌、乳球菌等益生菌增殖,对沙门氏菌、金黄色葡萄球菌、绿脓杆菌等有害细菌具有明显抑制作用;该人乳铁蛋白突变体可与长双歧杆菌配合使用,显著提高机体免疫球蛋白水平,降低氧自由基含量,防止氧化应激对人体造成损伤;所述人乳铁蛋白突变体及其组合物可口服使用,为保健食品和保健品的开发提供了新途径。
Description
技术领域
本发明属于生物技术领域,具体涉及一种人乳铁蛋白突变体及其与双歧杆菌在制备食品或保健品中的应用。
背景技术
免疫力是人体自身的防御机制,是人体识别和消灭外来侵入的任何异物(如病毒、细菌等)、处理衰老、损伤、死亡、变性的自身细胞以及识别和处理体内突变细胞和病毒感染细胞的能力。免疫力低下者更容易被感染或患病,常常变现为体质虚弱、营养不良、精神萎靡、疲乏无力、食欲降低、睡眠障碍等状态,严重者还会影响身体和智力发育,诱发腹泻、感冒、哮喘、肿瘤等严重疾病。提高机体免疫力是增强体质,改善机体免疫环境的重要方面,也是食品研究、保健品开发的重要研究方向,其中具有免疫调节功能的蛋白质和益生菌的应用受到研究人员的高度重视。
乳铁蛋白(Lactoferrin,LF),又称乳转铁蛋白(Lactotransferrin,LTF),分子量约为80kDa,属于铁结合蛋白家族成员,是一类非血红素铁结合的糖基化蛋白,在其氨基酸结构呈现“二枚银杏叶型”,分别在其分子的N端和C端形成2个环状结构(loops),每叶在内部缝隙处都有一个铁结合位点。乳铁蛋白于20世纪处被首次从牛乳中分离出来,因其晶体呈红色,能够高亲和性可逆地与铁结合,因此被称为乳铁蛋白。乳铁蛋白在母乳中的含量非常丰富,据报道可高达7g/L,是母乳中含量最丰富的蛋白之一。需要说明的是,乳铁蛋白不仅仅存在于动物乳汁中,而是广泛存在于多种组织及其分泌液中,包括但不限于动物乳汁、血液、泪液、粘液等,其具有丰富多样的生物学功能,包括抗菌、抗病毒、抗氧化、参与免疫调节、促进铁元素吸收等等;此外,乳铁蛋白为天然乳汁中的主要成分之一,对于胃肠消化系统的适应性较强,通常的服用过程中可采用口服方式,如Heidi Chan等(A randomized,double-blind,placebo-controlled trial to determine the efficacy and safety oflactoferrin with vitamin E and zinc as an oral therapy for mild to moderateacne vulgaris,International Journal of Dermatology,2017,56(6):686-690)、Mahmoud A El-Hawy等(Comparing oral iron bisglycinate chelate,lactoferrin,lactoferrin with iron and iron polymaltose complex in the treatment ofchildren with iron deficiency anemia,Clin Nutr ESPEN,2021,46:367-371)、阿拉腾珠拉等(裂壶藻和乳铁蛋白对大肠杆菌K99攻毒哺乳犊牛腹泻、生长性能、粪便评分及血清抗氧化指标的影响,动物营养学报,2020,32(9):4166-4176)均公开了使用口服方式研究乳铁蛋白的生理功能,这也为基于乳铁蛋白的食品或保健品的开发提供了方便,避免了一般免疫调节蛋白易被消化道破坏而难以直接开发制作食品或保健品的困境。然而,天然的牛乳或人乳中的乳铁蛋白在免疫调节方面的活性仍有待提高,尤其是与益生菌协同作用方面有待于改善和加强。
益生菌是通过定殖在人体内,改变宿主某一部位菌群组成的一类对宿主有益的活性微生物,通过调节宿主黏膜与系统免疫功能或通过调节肠道内菌群平衡,促进营养吸收保持肠道健康,产生有利于健康作用的单微生物或组成明确的混合微生物,其生理功能相当丰富,包括促进营养物质的消化吸收、提高机体免疫力、维持肠道菌群结构平衡和防止消化道炎症、对抗氧化应激等等。从益生菌的种类来看,人体中的益生菌主要包括酵母菌、益生芽孢菌、丁酸梭菌、乳杆菌、双歧杆菌、放线菌等。其中双歧杆菌是发现较早,应用最为广泛的益生菌,早在1899年法国巴斯德研究所的儿科医生Henry Tissier从母乳喂养的健康婴儿的粪便中分离出的一种厌氧的革兰氏阳性杆菌,因其一端有时呈分叉状,故命名为双歧杆菌(Bacillus bifidus)。相关研究结果表明,双歧杆菌具有营养作用、抗肿瘤作用、免疫增强作用、改善胃肠道功能、抗衰老等多种重要的生理功能,被广泛应用于食品、保健品和药品研发领域。然而单独使用双歧杆菌,往往效果差强人意,因而迫切需要获得可与之联合使用,大幅度改善免疫功能的新型生物制剂。
本发明基于上述现有技术中存在的问题,提供了一种具有全新氨基酸结构的乳铁蛋白突变体,与天然乳铁蛋白相比,可以显著提高双歧杆菌的增殖能力,抑制致病菌生长;并且适合与双歧杆菌构成复合制剂,大幅度提升机体免疫能力,帮助机体消除氧自由基过量导致的不良后果,为相关食品和保健品的开发提供了新的思路和途径。
发明内容
本发明的主要目的是提供一种提高机体免疫力的方式,具体提供了一种人乳铁蛋白突变体,可增强对双歧杆菌的促增殖能力;该乳铁蛋白与双歧杆菌构成组合物,口服使用后,可大幅度提高机体免疫能力,对抗氧自由基能力也有所提高,可全面提升机体的防御机能,为现代食品和保健品的开发提供了新手段。
本发明的详细技术方案如下:
提供了一种人乳铁蛋白突变体,其氨基酸序列如SEQ ID NO:1所示。
所述人乳铁蛋白突变体,以人源乳铁蛋白为基础,利用生物信息学手段和已有人乳铁蛋白结构解析数据,设计相应的定点突变,经过分子水平和细胞水平实验验证筛选而得,相对于野生型蛋白,在促进双歧杆菌增殖、提高机体免疫力和清除机体内氧自由基方面均展现出技术优势。
提供了一种编码所述人乳铁蛋白突变体基因,
进一步的,所述基因的核苷酸序列如SEQ ID NO:2所示。
提供了一种编码所述人乳铁蛋白突变体基因的重组载体。
提供了一种含有上述载体的宿主细胞。
进一步的,所述宿主细胞为大肠杆菌、酵母菌或昆虫细胞
提供了一种组合物,包括本发明中所述的人乳铁蛋白突变体和益生菌,所述益生菌选自双歧杆菌、乳杆菌和/或乳酸菌中的至少一种。
进一步的,所述益生菌选自长双歧杆菌和/或短双歧杆菌中的至少一种。
进一步的,所述益生菌为长双歧杆菌。
据报道,乳铁蛋白可促进双歧杆菌、乳球菌、乳杆菌等益生菌生长,而对于包括沙门氏菌、金黄色葡萄球菌、绿脓杆菌在内的大多数有害细菌却展现出较强的抑制作用,因而其在肠道菌群调解方面具有一定的选择性。即使是对于益生菌类,乳铁蛋白对于不同种类的益生菌也展现了不同程度的促进作用,因此在本发明中经过严格实验验证和筛选,最终确定所述人乳铁蛋白突变体与长双歧杆菌的组合在改善机体免疫力方面最为有效,有望在相关食品或保健品开发中发挥更大作用。
提供了一种所述人乳铁蛋白突变体、基因、重组载体、宿主细胞或组合物在制备食品中的应用。
提供了一种所述人乳铁蛋白突变体、基因、重组载体、宿主细胞或组合物在制备保健品中的应用。
与现有技术相比,本发明的有益效果为:
本发明提供了一种新型人乳铁蛋白突变体,具有全新的氨基酸结构,能够显著促进双歧杆菌、乳杆菌、乳球菌等益生菌增殖,对沙门氏菌、金黄色葡萄球菌、绿脓杆菌等有害细菌具有明显抑制作用,而且该蛋白保留了人乳铁蛋白可口服使用的特性,为保健食品和保健品的开发提供了便利;所述人乳铁蛋白突变体与长双歧杆菌构成组合物,能够大幅度提升机体免疫能力,快速清除体内过量的氧自由基,维持机体内环境平衡。
附图说明
图1人乳铁蛋白突变体对益生菌的生长促进作用;
图2人乳铁蛋白突变体对有害菌的生长抑制作用;
图3乳铁蛋白与长双歧杆菌组合物对免疫球蛋白的影响;
图4乳铁蛋白与长双歧杆菌组合物对ROS的影响;
具体实施方式
以下非限制性实施例可以使本领域的普通技术人员更全面地理解本发明,但不以任何形式限制本发明。凡基于本发明上述内容所实现的技术均应当属于本申请要求保护的范围之中。
以下实施例中所述实验方法,如无特殊说明,均为常规方法;所述试剂生物材料、检测试剂盒,如无特殊说明,均可从商业途径获得。
实施例1人乳铁蛋白突变体的确定和制备
所述人乳铁蛋白突变体,以人源乳铁蛋白为基础,利用生物信息学手段和已有人乳铁蛋白结构解析数据,设计相应的定点突变,经过分子水平和细胞水平实验验证筛选而得,经鉴定所述人乳铁蛋白突变体的氨基酸序列如SEQ ID No.1所示,其核苷酸序列如SEQID No.2所示。
以大肠杆菌为宿主菌制备本发明中所述的人乳铁蛋白突变体。首先设计上下游PCR引物扩增人乳铁蛋白突变体(以下简称mu-hLF)基因,并在上下游引物中分别引入EcoRI和XhoI酶切位点;其次用EcoRI和XhoI双酶切表达载体pET28a和mu-hLF基因片段,酶切连接后得到重组表达载体pET28a-mu-hLF,然后将该重组表达载体电转化导入宿主菌E.coliBL21(DE3)中;在5L生物反应器中培养上述宿主菌,达到对数生长状态后,流加输入诱导剂IPTG,诱导表达生产目标蛋白,诱导表达16-24h后,4℃、8000rpm离心收集菌体,超声破碎后通过亲和层析色谱柱分离获得重组人乳铁蛋白突变体蛋白,经高效液相色谱鉴定所述蛋白纯度达98%以上,满足后续实验要求。
实施例2重组人乳铁蛋白突变体对不同微生物生长的影响
2.1重组人乳铁蛋白突变体促进益生菌生长
取冻存的双歧杆菌(包括长双歧杆菌和短双歧杆菌)、乳杆菌、乳球菌菌株,上述菌株本实验室保存,复苏后接种与无菌LB培养基中活化培养24小时;离心收集菌体,使用无菌LB培养基调整菌体浓度至1×105CFU/mL,分别取上述4种益生菌1mL接种于20mL无菌LB培养基中;将各个益生菌分为三组,分别加入50mg/mL的mu-hLF蛋白、50mg/mL天然人乳铁蛋白(以下简称hLF)和等体积的无菌水(作为空白对照),于摇床上37℃培养24后,使用分光光度计测量OD600数值。
结果如图1所示,天然和突变的人乳铁蛋白均能够促进双歧杆菌、乳杆菌和乳球菌生长,但是本发明中所提供的mu-hLF在促进双歧杆菌生长方面具有明显优势,在添加mu-hLF的培养液中双歧杆菌的数量远高于hLF组和对照组,尤其是对于长双歧杆菌,这种促增殖作用更加明显;但在乳杆菌和乳球菌中,虽然mu-hLF也有明显的生长促进作用,但是相比于天然hLF未见显著差异。
2.2重组人乳铁蛋白突变体抑制有害菌生长
取沙门氏菌、金黄色葡萄球菌、绿脓杆菌、产气荚膜梭菌菌株(本实验室保存),验证人乳铁蛋白对其抑制作用,具体实验步骤同2.1节。结果图2所示,天然人乳铁蛋白和突变修饰的人乳铁蛋白具有展现出了对多四种有害微生物的抑制作用,其中在绿脓杆菌中,mu-hLF的抑制作用似乎强于天然人乳铁蛋白,但在其他三种有害细菌中二者取未见显著差异。
实施例3重组人乳铁蛋白与双歧杆菌组合物的制备
本实施例中选择在前期实验中促增殖作用最强的长双歧杆菌菌,与人乳铁蛋白突变体制成组合物,用于验证其体内服用效果,具体步骤如下:
首先制备mu-hLF蛋白和hLF蛋白,具体步骤参考实施例1,将获得的蛋白冷冻干燥,获得蛋白质粉;其次制备长双歧杆菌菌粉,将长双歧杆菌接种于无菌LB培养基中活化培养约24h,将活化后的菌体接种于5L生物反应器中,37℃下进行培养,每小时检测pH和OD值,待其生长状态进入稳定期后结束发酵,低温离心、收集菌体,磷酸盐缓冲液(PBS)洗涤后,加冻干保护剂(脱脂奶粉)后进行乳化,完成后进行真空冷冻干燥,得到长双歧杆菌菌粉;最后制备人乳铁蛋白与长双歧杆菌组合物,将上述两种组分按照1:10比例混合,分别获得mu-hLF-Bp组合物和hLF-Bp组合物。
实施例4重组人乳铁蛋白与双歧杆菌组合物的体内实验
为验证本发明中所提供的mu-hLF蛋白与益生菌联合改善机体免疫机能的效果,本实施例中采用大鼠模型,口服人乳铁蛋白与双歧杆菌组合物后,考察其对于免疫能力的影响。
4.1实验动物处理
选取健康SD大鼠,SPF级,雌雄各半,体重180±20g,随机分组,每组10只,共3组,包括生理盐水组、mu-hLF-Bp组、hLF-Bp组,其中mu-hLF-Bp组每日口服100mg/kg的mu-hLF-Bp组合物,hLF-Bp组每日口服100mg/kg的hLF-Bp组合物,生理盐水组每日口服1mL无菌生理盐水,共口服30天后进行检测。
4.2机体免疫能力检测
免疫球蛋白是具有抗体活性的,与抗体分子相似的球蛋白,它是机体免疫的重要组成部分,可帮助机体对抗多种有害物质的侵袭,包括细菌、病毒、有害异物等等,免疫球蛋白分为五类,即免疫球蛋白G(IgG)、免疫球蛋白A(IgA)、免疫球蛋白M(IgM)、免疫球蛋白D(IgD)和免疫球蛋白E(IgE),其中IgG、IgA、IgM在血清中的含量较多,其生理活性也最为重要,因此本实施例中通过检测上述三种免疫球蛋白的含量来考察对于机体免疫能力的影响。
大鼠尾静脉取血,将全血以3000rpm的速率离心10min。吸取上清液,采用IgA、IgG、IgM免疫球蛋白试剂盒(购自南京建成生物公司)检测血液中IgA、IgG、IgM含量,结果如图3所示,乳铁蛋白和长双歧杆菌构成的组合物对于上述三种免疫球蛋白浓度均有提升作用,但是在IgM方面,mu-hLF-Bp组合物相比于hLF-Bp组合物并没有展现出更多优势,血液中的IgM水平没有显著变化;在IgA、IgG方面,使用人乳铁蛋白突变体与双歧杆菌组合,则能够显著增加相应的免疫球蛋白水平。
众所周知,IgG是血清中免疫球蛋白的主成分,约占血清中免疫球蛋白总含量的75%,是体内最主要的抗体,具有抗病毒、中和病毒、抗菌及免疫调节的功能。IgA是血清中的含量仅次于IgG,占血清免疫球蛋白的10~20%,多存在于黏膜组织,如消化道、呼吸道、泌尿生殖系统等,也具有强大的抗菌、抗病毒和免疫调节功能。本申请中所提供的mu-hLF-Bp组合物能够显著提升IgA、IgG水平,说明其能够有效激活和促进机体的自身免疫水平,进而有效预防外界有害物质的侵袭和干扰。
4.3抗氧化能力检测
活性氧(reactive oxygen species,ROS)是体内一类氧的单电子还原产物,是线粒体由状态Ⅲ向状态Ⅳ转换中高氧的环境和高还原态的呼吸链使大量电子漏出并还原氧分子而形成。活性氧是机体内正常代谢的产物,具有积极作用,如辅助吞噬细胞发挥杀伤作用,但是当其含量升高,造成活性氧的产生和清除失衡,则会引起活性氧对人体中的核苷酸、蛋白质、细胞膜造成广泛的损伤,从而引发多种疾病。
本实施例中为研究所述组合物对ROS的作用效果,使用试剂盒(购自南京建成生物公司)检测血清中活性氧含量。结果如图4所示,mu-hLF-Bp组合物可显著降低血清中ROS含量,其作用效果强于hLF-Bp组合物,表明这种联合使用可产生有效的协同作用,清除体内过量的氧自由基,保护机体免疫氧化应激损伤。
以上所述实施例仅表达了本发明的几种实施方式,其描述较为具体和详细但并不能因此而理解为对发明专利范围的限制。应当指出的是,对于本领域的普通技术人员来说,在不脱离本发明构思的前提下,还可以做出若干变形和改进,这些都属于本发明的保护范围。
序列表
<110> 广州泰术生物科技有限公司
<120> 一种人乳铁蛋白突变体及其与双歧杆菌在制备食品或保健品中的应用
<160> 2
<170> SIPOSequenceListing 1.0
<210> 1
<211> 709
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 1
Met Lys Leu Val Phe Leu Val Leu Leu Phe Leu Gly Ala Lys Gly Leu
1 5 10 15
Cys Leu Ala Gly Arg Arg Arg Gly Ser Val Lys Asn Cys Ala Thr Ser
20 25 30
Gln Pro Glu Ala Thr Lys Cys Phe Gln Trp Gln Arg Asn Met Arg Arg
35 40 45
Val Arg Gly Pro Pro Val Ser Cys Ile Lys Arg Asp Ser Pro Ile Gln
50 55 60
Cys Trp Met Ala Ile Ala Gly Asn Arg Ala Asp Ala Val Thr Leu Asp
65 70 75 80
Gly Gly Phe Ile Tyr Glu Ala Gly Leu Ala Pro Tyr Lys Leu Arg Pro
85 90 95
Val Ala Ala Glu Val Tyr Gly Thr Glu Arg Gln Pro Arg Thr His Tyr
100 105 110
Tyr Ala Val Ala Val Val Lys Lys Gly Gly Ser Phe Gln Leu Asn Glu
115 120 125
Leu Gln Gly Leu Lys Ser Cys His Thr Gly Leu Arg Arg Thr Ala Gly
130 135 140
Trp Asn Val Pro Ile Gly Thr Leu Arg Pro Phe Leu Asn Trp Thr Gly
145 150 155 160
Pro Pro Glu Pro Ile Glu Ala Ala Val Ala Arg Phe Phe Ser Ala Ser
165 170 175
Cys Val Pro Gly Ala Asp Lys Gly Gln Phe Pro Asn Leu Cys Arg Leu
180 185 190
Cys Ala Gly Thr Gly Glu Asn Lys Cys Ala Phe Ser Ser Gln Glu Pro
195 200 205
Tyr Phe Ser Tyr Ser Gly Ala Phe Lys Cys Leu Arg Asp Gly Ala Gly
210 215 220
Asp Val Ala Phe Ile Arg Glu Ser Thr Val Phe Glu Asp Leu Thr Met
225 230 235 240
Glu Ala Glu Ala Asp Glu Gln Glu Leu Leu Cys Pro Asp Asn Thr Arg
245 250 255
Lys Pro Val Asp Lys Phe Lys Asp Cys His Leu Ala Arg Val Pro Ser
260 265 270
His Ala Val Val Ala Arg Ser Val Asn Gly Lys Glu Asp Ala Ile Trp
275 280 285
Asn Leu Leu Arg Gln Ala Gln Glu Lys Phe Gly Lys Asp Lys Ser Pro
290 295 300
Lys Phe Gln Leu Phe Gly Ser Pro Ser Gly Gln Lys Asp Leu Leu Phe
305 310 315 320
Lys Asp Ser Ala Ile Gly Ser Ser Arg Val Pro Pro Arg Ile Asp Ser
325 330 335
Gly Leu Tyr Leu Gly Ser Gly Tyr Phe Thr Ala Ile Gln Asn Leu Arg
340 345 350
Lys Ser Glu Glu Glu Val Ala Ala Arg Arg Ala Arg Val Val Trp Cys
355 360 365
Ala Val Gly Glu Gln Glu Leu Arg Lys Cys Asn Gln Trp Ser Gly Leu
370 375 380
Ser Glu Gly Ser Val Thr Cys Ser Ser Ala Ser Thr Thr Glu Asp Cys
385 390 395 400
Ile Ala Leu Lys Gly Glu Ala Asp Ala Met Ser Leu Asp Gly Gly Tyr
405 410 415
Val Tyr Thr Ala Gly Lys Cys Gly Leu Val Pro Val Leu Ala Glu Asn
420 425 430
Tyr Lys Ser Gln Gln Ser Ser Asp Pro Asp Pro Asn Cys Val Asp Arg
435 440 445
Pro Val Glu Gly Tyr Leu Ala Val Ala Val Val Arg Arg Ser Asp Thr
450 455 460
Ser Leu Thr Trp Asn Ser Val Lys Gly Lys Lys Ser Cys His Thr Ala
465 470 475 480
Val Asp Arg Thr Ala Gly Trp Asn Ile Pro Met Gly Leu Leu Phe Asn
485 490 495
Gln Thr Gly Ser Cys Lys Phe Asp Glu Tyr Phe Ser Gln Ser Cys Ala
500 505 510
Pro Gly Ser Asp Pro Arg Ser Asn Leu Cys Ala Leu Cys Ile Gly Asp
515 520 525
Glu Thr Gly Met Asn Lys Trp Val Pro Asn Ser Asn Glu Ser Tyr Tyr
530 535 540
Glu Tyr Thr Gly Ala Phe Arg Cys Leu Ala Glu Asn Ala Gly Asp Val
545 550 555 560
Ala Phe Val Lys Asp Val Thr Val Leu Gln Asn Thr Asp Gly Asn Asn
565 570 575
Asn Asp Ala Trp Ala Lys Asp Leu Lys Leu Ala Asp Phe Ala Leu Leu
580 585 590
Cys Leu Asp Gly Lys Arg Lys Pro Val Thr Glu Ala Arg Ser Cys His
595 600 605
Leu Ala Met Ala Pro Asn His Ala Val Val Ser Arg Met Asp Lys Val
610 615 620
Glu Arg Leu Lys Gln Val Leu Leu His Gln Gln Ala Lys Phe Gly Arg
625 630 635 640
Asn Gly Ser Asp Cys Pro Asp Lys Phe Cys Leu Phe Gln Ser Glu Thr
645 650 655
Lys Asn Leu Leu Phe Asn Asp Asn Thr Glu Cys Leu Ala Arg Leu His
660 665 670
Gly Lys Thr Thr Tyr Glu Lys Tyr Leu Gly Pro Gln Tyr Val Ala Gly
675 680 685
Ile Thr Asn Leu Lys Lys Cys Ser Thr Ser Pro Leu Leu Glu Ala Cys
690 695 700
Glu Phe Leu Arg Lys
705
<210> 2
<211> 2127
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 2
atgaaactgg tgtttctggt gctgctgttt ctgggcgcga aaggcctgtg cctggcgggc 60
cgccgccgcg gcagcgtgaa aaactgcgcg accagccagc cggaagcgac caaatgcttt 120
cagtggcagc gcaacatgcg ccgcgtgcgc ggcccgccgg tgagctgcat taaacgcgat 180
agcccgattc agtgctggat ggcgattgcg ggcaaccgcg cggatgcggt gaccctggat 240
ggcggcttta tttatgaagc gggcctggcg ccgtataaac tgcgcccggt ggcggcggaa 300
gtgtatggca ccgaacgcca gccgcgcacc cattattatg cggtggcggt ggtgaaaaaa 360
ggcggcagct ttcagctgaa cgaactgcag ggcctgaaaa gctgccatac cggcctgcgc 420
cgcaccgcgg gctggaacgt gccgattggc accctgcgcc cgtttctgaa ctggaccggc 480
ccgccggaac cgattgaagc ggcggtggcg cgctttttta gcgcgagctg cgtgccgggc 540
gcggataaag gccagtttcc gaacctgtgc cgcctgtgcg cgggcaccgg cgaaaacaaa 600
tgcgcgttta gcagccagga accgtatttt agctatagcg gcgcgtttaa atgcctgcgc 660
gatggcgcgg gcgatgtggc gtttattcgc gaaagcaccg tgtttgaaga tctgaccatg 720
gaagcggaag cggatgaaca ggaactgctg tgcccggata acacccgcaa accggtggat 780
aaatttaaag attgccatct ggcgcgcgtg ccgagccatg cggtggtggc gcgcagcgtg 840
aacggcaaag aagatgcgat ttggaacctg ctgcgccagg cgcaggaaaa atttggcaaa 900
gataaaagcc cgaaatttca gctgtttggc agcccgagcg gccagaaaga tctgctgttt 960
aaagatagcg cgattggcag cagccgcgtg ccgccgcgca ttgatagcgg cctgtatctg 1020
ggcagcggct attttaccgc gattcagaac ctgcgcaaaa gcgaagaaga agtggcggcg 1080
cgccgcgcgc gcgtggtgtg gtgcgcggtg ggcgaacagg aactgcgcaa atgcaaccag 1140
tggagcggcc tgagcgaagg cagcgtgacc tgcagcagcg cgagcaccac cgaagattgc 1200
attgcgctga aaggcgaagc ggatgcgatg agcctggatg gcggctatgt gtataccgcg 1260
ggcaaatgcg gcctggtgcc ggtgctggcg gaaaactata aaagccagca gagcagcgat 1320
ccggatccga actgcgtgga tcgcccggtg gaaggctatc tggcggtggc ggtggtgcgc 1380
cgcagcgata ccagcctgac ctggaacagc gtgaaaggca aaaaaagctg ccataccgcg 1440
gtggatcgca ccgcgggctg gaacattccg atgggcctgc tgtttaacca gaccggcagc 1500
tgcaaatttg atgaatattt tagccagagc tgcgcgccgg gcagcgatcc gcgcagcaac 1560
ctgtgcgcgc tgtgcattgg cgatgaaacc ggcatgaaca aatgggtgcc gaacagcaac 1620
gaaagctatt atgaatatac cggcgcgttt cgctgcctgg cggaaaacgc gggcgatgtg 1680
gcgtttgtga aagatgtgac cgtgctgcag aacaccgatg gcaacaacaa cgatgcgtgg 1740
gcgaaagatc tgaaactggc ggattttgcg ctgctgtgcc tggatggcaa acgcaaaccg 1800
gtgaccgaag cgcgcagctg ccatctggcg atggcgccga accatgcggt ggtgagccgc 1860
atggataaag tggaacgcct gaaacaggtg ctgctgcatc agcaggcgaa atttggccgc 1920
aacggcagcg attgcccgga taaattttgc ctgtttcaga gcgaaaccaa aaacctgctg 1980
tttaacgata acaccgaatg cctggcgcgc ctgcatggca aaaccaccta tgaaaaatat 2040
ctgggcccgc agtatgtggc gggcattacc aacctgaaaa aatgcagcac cagcccgctg 2100
ctggaagcgt gcgaatttct gcgcaaa 2127
Claims (10)
1.一种人乳铁蛋白突变体,其特征在于,其氨基酸序列如SEQ ID No.1所示。
2.一种编码权利要求1所述人乳铁蛋白突变体的基因,其核苷酸序列如SEQ ID No.2所示。
3.一种含有权利要求2所述的基因的重组载体。
4.一种含有权利要求3所述的重组载体的宿主细胞。
5.根据权利要求4所述的宿主细胞,其特征在于所述宿主细胞为大肠杆菌、酵母菌或昆虫细胞。
6.一种组合物,包括权利要求1中所述的人乳铁蛋白突变体和益生菌,所述益生菌为乳酸菌。
7.根据权利要求6所述的组合物,其特征在于所述益生菌选自双歧杆菌和/或乳杆菌。
8.根据权利要求7所述的组合物,其特征在于当益生菌选自双歧杆菌时,双歧杆菌选自长双歧杆菌和/或短双歧杆菌中的至少一种。
9.一种如权利要求1中所述的人乳铁蛋白突变体或权利要求2所述的基因或权利要求3所述的重组载体或权利要求4-5所述的宿主细胞或权利要求6-8中所述组合物在制备食品中的应用。
10.一种如权利要求1中所述的人乳铁蛋白突变体或权利要求2所述的基因或权利要求3所述的重组载体或权利要求4-5所述的宿主细胞或权利要求6-8中所述组合物在制备保健品中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210378074.3A CN114716538B (zh) | 2022-04-12 | 2022-04-12 | 一种人乳铁蛋白突变体及其与双歧杆菌在制备食品或保健品中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210378074.3A CN114716538B (zh) | 2022-04-12 | 2022-04-12 | 一种人乳铁蛋白突变体及其与双歧杆菌在制备食品或保健品中的应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114716538A CN114716538A (zh) | 2022-07-08 |
CN114716538B true CN114716538B (zh) | 2023-05-12 |
Family
ID=82243361
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210378074.3A Active CN114716538B (zh) | 2022-04-12 | 2022-04-12 | 一种人乳铁蛋白突变体及其与双歧杆菌在制备食品或保健品中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114716538B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114711434B (zh) * | 2022-04-12 | 2023-07-21 | 河北雄安重生生物科技有限公司 | 一种人乳铁蛋白突变体及其联合乳杆菌在制备食品或保健品中的应用 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001032895A1 (en) * | 1999-10-19 | 2001-05-10 | Easy Bio System, Inc. | Recombinant yeast strain for expressing human lactoferrin, n-lobe lactoferrin, c-lobe lactoferrin and process for preparation recombinant human lactoferrin, n-lobe lactoferrin, c-lobe lactoferrin using the same |
CN111499759B (zh) * | 2019-01-31 | 2022-12-20 | 上海科技大学 | 一种具有细胞穿膜性的锌指蛋白-乳铁蛋白融合蛋白质及其制备与应用 |
CN112500475B (zh) * | 2020-12-30 | 2022-05-03 | 广州暨南大学医药生物技术研究开发中心有限公司 | 类人乳铁蛋白肽及其应用 |
-
2022
- 2022-04-12 CN CN202210378074.3A patent/CN114716538B/zh active Active
Also Published As
Publication number | Publication date |
---|---|
CN114716538A (zh) | 2022-07-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR102138834B1 (ko) | 락토바실러스 가세리 kbl697 균주 및 그 용도 | |
CA2521220C (en) | Compositions comprising lactobacillus plantarum strains in combination with tannin and new lactobacillus plantarum strains | |
Drago-Serrano et al. | Lactoferrin increases both resistance to Salmonella typhimurium infection and the production of antibodies in mice | |
KR101164876B1 (ko) | 브로콜리를 유산균으로 발효한 항염 및 항헬리코박터의 효과가 있는 기능성 발효물질 및 이의 제조방법 | |
CN106413724B (zh) | 与多糖聚合物粘合剂缀合的鼠李糖乳杆菌rht-3201及其用途 | |
EP3565582B1 (en) | Microbial lysozyme for use in the treatment of irritable bowel syndrome or inflammatory bowel disease | |
Singh et al. | Antimicrobial activity of bioactive peptides derived from fermentation of soy milk by Lactobacillus plantarum C2 against common foodborne pathogens | |
US20220000950A1 (en) | Compositions and Methods of Use of Novel Strains of Lactobacillus Fermentum | |
CN114716538B (zh) | 一种人乳铁蛋白突变体及其与双歧杆菌在制备食品或保健品中的应用 | |
CN114711434B (zh) | 一种人乳铁蛋白突变体及其联合乳杆菌在制备食品或保健品中的应用 | |
Ren et al. | In vivo assessment of immunomodulatory activity of hydrolysed peptides from Corylus heterophylla Fisch | |
KR100988771B1 (ko) | 엔테로코쿠스 및 스트렙토코쿠스 특이적 사멸능을 갖는 신규한 리신 단백질 | |
KR101910808B1 (ko) | 유산균 유래 p8 단백질 및 이의 항암 용도 | |
Wang et al. | Effects of vinegar–egg on growth inhibition, differentiation human leukemic U937 cells and its immunomodulatory activity | |
Mahdi | Immunomodulatory of Bifidobacterium breve and inhibitory effect of bifidobrevicin-lhm on Streptococcus agalactiae and its β-hemolysin | |
WO2011065300A1 (ja) | 抗ウイルス剤及び飲食品組成物 | |
KR20180087662A (ko) | 유산균 유래 단백질 및 시스타틴을 포함하는 대장질환 치료용 약학조성물 | |
EP1002539A1 (en) | Immunomodulator comprising bacterial cells or cell wall decomposition products thereof | |
JP3995733B2 (ja) | 免疫賦活組成物 | |
KR20170127800A (ko) | 면역 조절 t 세포를 유도하는 락토코커스 락티스 bfe920 균주를 포함하는 수산양식 기능성 사료 첨가제 | |
Atta et al. | Application of biotechnology for production, purification and characterization of peptide antibiotic produced by probiotic Lactobacillus plantarum, NRRL B-227 | |
RU2304167C2 (ru) | Способ получения гликопептидов и гликопептидный продукт, полученный этим способом, для использования в медицине | |
WO2022200851A1 (en) | Lactobacillus delbrueckii subsp. lactis ldl557 isolate, and composition including the same and use thereof | |
Yang et al. | Inhibitory action of soybean β-conglycinin hydrolysates on Salmonella typhimurium translocation in Caco-2 epithelial cell monolayers | |
Akther et al. | Optimizing the fermentation condition of low salted squid jeotgal by lactic acid bacteria with enhanced antioxidant activity |
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 | ||
TA01 | Transfer of patent application right | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20230420 Address after: 201100 Building 2, 889 Qishen Road, Minhang District, Shanghai Applicant after: Zaozuo Technology Co.,Ltd. Address before: Room 1004f, No. 403, Huanshi East Road, Yuexiu District, Guangzhou, Guangdong 510000 Applicant before: Guangzhou Taizhu Biotechnology Co.,Ltd. |
|
GR01 | Patent grant | ||
GR01 | Patent grant |