CN112442108A - 一种枸杞ace、dpp-iv抑制肽及衍生多肽和应用、混合物 - Google Patents
一种枸杞ace、dpp-iv抑制肽及衍生多肽和应用、混合物 Download PDFInfo
- Publication number
- CN112442108A CN112442108A CN201910806960.XA CN201910806960A CN112442108A CN 112442108 A CN112442108 A CN 112442108A CN 201910806960 A CN201910806960 A CN 201910806960A CN 112442108 A CN112442108 A CN 112442108A
- Authority
- CN
- China
- Prior art keywords
- polypeptide
- dpp
- ace
- llepigvvgh
- inhibitor
- 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.)
- Granted
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 61
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 47
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 42
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 42
- 235000017784 Mespilus germanica Nutrition 0.000 title claims abstract description 15
- 235000000560 Mimusops elengi Nutrition 0.000 title claims abstract description 15
- 235000007837 Vangueria infausta Nutrition 0.000 title claims abstract description 15
- 240000002624 Mespilus germanica Species 0.000 title claims abstract 3
- 239000000203 mixture Substances 0.000 title claims description 4
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 title 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 title 1
- 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 claims abstract description 49
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 claims abstract description 49
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 claims abstract description 37
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 claims abstract description 37
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000003814 drug Substances 0.000 claims abstract description 9
- 235000013376 functional food Nutrition 0.000 claims abstract description 8
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 4
- 150000001875 compounds Chemical class 0.000 claims abstract 3
- 239000003112 inhibitor Substances 0.000 claims description 9
- 239000008280 blood Substances 0.000 claims description 6
- 210000004369 blood Anatomy 0.000 claims description 6
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 239000002220 antihypertensive agent Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000005541 ACE inhibitor Substances 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 4
- 239000003937 drug carrier Substances 0.000 claims 3
- 230000003276 anti-hypertensive effect Effects 0.000 claims 2
- 239000003472 antidiabetic agent Substances 0.000 claims 2
- 230000004531 blood pressure lowering effect Effects 0.000 claims 2
- 229940126904 hypoglycaemic agent Drugs 0.000 claims 2
- 238000000338 in vitro Methods 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 1
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 claims 1
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 claims 1
- 208000001953 Hypotension Diseases 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 229940030600 antihypertensive agent Drugs 0.000 claims 1
- 208000021822 hypotensive Diseases 0.000 claims 1
- 230000001077 hypotensive effect Effects 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 abstract description 25
- 108090000623 proteins and genes Proteins 0.000 abstract description 25
- 230000036772 blood pressure Effects 0.000 abstract description 10
- 238000000855 fermentation Methods 0.000 abstract description 6
- 230000004151 fermentation Effects 0.000 abstract description 6
- 230000001105 regulatory effect Effects 0.000 abstract description 5
- 238000000034 method Methods 0.000 abstract description 4
- 235000018102 proteins Nutrition 0.000 description 25
- 239000000243 solution Substances 0.000 description 20
- 238000002835 absorbance Methods 0.000 description 18
- 244000182216 Mimusops elengi Species 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 239000012488 sample solution Substances 0.000 description 11
- 239000000523 sample Substances 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000000872 buffer Substances 0.000 description 8
- 239000007853 buffer solution Substances 0.000 description 8
- 244000241838 Lycium barbarum Species 0.000 description 7
- 235000015459 Lycium barbarum Nutrition 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 102000007079 Peptide Fragments Human genes 0.000 description 6
- 108010033276 Peptide Fragments Proteins 0.000 description 6
- 150000001413 amino acids Chemical group 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 230000008859 change Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 238000004949 mass spectrometry Methods 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 101000984728 Chiropsoides quadrigatus Angiotensin-converting enzyme inhibitory peptide Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 3
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 3
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000000975 bioactive effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 201000001421 hyperglycemia Diseases 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 2
- ZDLZKMDMBBMJLI-FDMDGMSGSA-N 2-[[2-[[(2s)-2-[[(e)-3-(furan-2-yl)prop-2-enoyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]acetic acid Chemical compound C([C@@H](C(=O)NCC(=O)NCC(=O)O)NC(=O)\C=C\C=1OC=CC=1)C1=CC=CC=C1 ZDLZKMDMBBMJLI-FDMDGMSGSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- 108010048632 2-furanacryloyl-phenylalanyl-glycyl-glycine Proteins 0.000 description 2
- 244000063299 Bacillus subtilis Species 0.000 description 2
- 235000014469 Bacillus subtilis Nutrition 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 238000011033 desalting Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000012089 stop solution Substances 0.000 description 2
- 238000005556 structure-activity relationship Methods 0.000 description 2
- 238000004885 tandem mass spectrometry Methods 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 1
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 108010008488 Glycylglycine Proteins 0.000 description 1
- QNBVTHNJGCOVFA-AVGNSLFASA-N Leu-Leu-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCC(O)=O QNBVTHNJGCOVFA-AVGNSLFASA-N 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 102000006833 Multifunctional Enzymes Human genes 0.000 description 1
- 108010047290 Multifunctional Enzymes Proteins 0.000 description 1
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 1
- GUCCBOQKNLHXEA-KCWXNJEJSA-N O1C(=CC=C1)C(=O)C=CC(=O)[C@](N(CCCCC)C1=CC=CC=C1)(CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O Chemical compound O1C(=CC=C1)C(=O)C=CC(=O)[C@](N(CCCCC)C1=CC=CC=C1)(CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O GUCCBOQKNLHXEA-KCWXNJEJSA-N 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108010064851 Plant Proteins Proteins 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
- 239000004365 Protease Substances 0.000 description 1
- 206010061481 Renal injury Diseases 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- AEFJNECXZCODJM-UWVGGRQHSA-N Val-Val-Gly Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](C(C)C)C(=O)NCC([O-])=O AEFJNECXZCODJM-UWVGGRQHSA-N 0.000 description 1
- 238000003916 acid precipitation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000005686 electrostatic field Effects 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 102000013370 fibrillin Human genes 0.000 description 1
- 108060002895 fibrillin Proteins 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- KZNQNBZMBZJQJO-YFKPBYRVSA-N glyclproline Chemical compound NCC(=O)N1CCC[C@H]1C(O)=O KZNQNBZMBZJQJO-YFKPBYRVSA-N 0.000 description 1
- 229940043257 glycylglycine Drugs 0.000 description 1
- 108010020688 glycylhistidine Proteins 0.000 description 1
- 108010077515 glycylproline Proteins 0.000 description 1
- 108010037850 glycylvaline Proteins 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000005040 ion trap Methods 0.000 description 1
- 208000037806 kidney injury Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 235000021118 plant-derived protein Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 230000036454 renin-angiotensin system Effects 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 208000023516 stroke disease Diseases 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Obesity (AREA)
- Food Science & Technology (AREA)
- Mycology (AREA)
- Polymers & Plastics (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Nutrition Science (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
本发明涉及一种利用枸杞蛋白通过发酵法制备血管紧张素转换酶(angiotensin‑converting enzyme,ACE)和二肽基肽酶(dipeptidyl peptidase IV,DPP‑IV)抑制活性的多肽。多肽LLEPIGVVGH，其氨基酸序列为Leu‑Leu‑Glu‑Pro‑Ile‑Gly‑Val‑Val‑Gly‑His，分子量为1033.24Da。其具有良好的ACE、DPP‑IV抑制活性，具有开发成为调节血压的功能性食品或者是药物的良好应用前景。
Description
技术领域
本发明涉及一种通过发酵法将枸杞蛋白质制备具有血管紧张素转换酶(angiotensin-converting enzyme,ACE)和二肽基肽酶(dipeptidyl peptidase IV,DPP-IV)抑制活性的多肽LLEPIGVVGH，其在调节血压的功能性食品和药物中的应用。
背景技术
高血压作为最常见的心脑血管疾病之一，是脑卒中、冠心病等心血管疾病最重要的危险因素。长期的高血糖会使全身各个组织器官发生病变，导致急慢性并发症的发生，如失水、电解质紊乱等。随着社会经济的高速发展，人们生活饮食结构的改变，高血压、高血糖的发病率也逐年增高，严重影响为我国居民身体健康。预防、治疗高血压、高血糖是当今社会面临的主要问题。
ACE作为一种多功能酶，广泛存在于人体中，通过作用于体内的肾素-血管紧张素系统(Renin-Angiotensin System,RAS)和激肽释放酶-激肽系统(Kallikrein-KininSystem,KKS)起到调节血压的功能。因此ACE抑制剂作为一种降血压药物被广泛利用。但由于化学合成西药类降压药物对于人体具有毒副作用，尤其药物吸收对于肝肾组织造成极大负担，引起肝肾损伤，并且停药后症状反复，愈后疗效不十分理想。
DPP-IV是一种细胞表面的丝氨酸蛋白酶，可以灭活多种生物活性肽，包括胰高血糖素样肽-1(glucagon-like peptide-1，GLP-1)。DPP-IV抑制剂通过使DPP-IV失活，提高体内GLP-1水平，产生调节血糖的作用。
生物活性肽是近年来的研究热点。天然蛋白在蛋白酶及微生物作用下会释放出不同结构的肽，研究表明生物活性肽表现出各种生物活性如降血压、降血糖、提高免疫力、抗菌、抗氧化等等。利用天然蛋白质制备ACE、DPP-IV抑制剂具有功能明确、安全性高的特点，因此无论作为功能食品还是药品具有广阔的前景。
本发明就是有关于发酵枸杞蛋白制备的一种ACE、DPP-IV抑制活性肽。
发明内容
本发明的目的是关于多肽LLEPIGVVGH对于ACE、DPP-IV抑制活性；其具有序列表SEQ ID NO：1中氨基酸序列；具有良好的ACE、DPP-IV抑制活性，通过抑制AC、DPP-IV活性起到降血压、降血糖的功能。并且具有开发成为调节血压、血糖的功能性食品或者是药物的良好应用前景。
为实现上述目的，本发明在充分利用枸杞蛋白的基础上，以产物多肽LLEPIGVVGH为主要成分，抑制ACE、DPP-IV的活性并且调节血压。在此基础上，多肽LLEPIGVVGH可以作为ACE、DPP-IV抑制剂，调节血压、血糖的药物和相关功能性成品的主要成分。
具有抑制ACE、DPP-IV活性和降血压活性的多肽LLEPIGVVGH，氨基酸序列为Leu-Leu-Glu-Pro-Ile-Gly-Val-Val-Gly-His，为单链线性结构，白色粉末状，易溶于水，分子量为1033.24Da；对ACE活性具有较强抑制作用，半抑制浓度(IC50)为215.24μM；对DPP-IV活性具有较强抑制作用，半抑制浓度(IC50)为208.29μM，
使用生物信息学软件Peptide(http://pepsite2.russelllab.org/)对于多肽LLEPIGVVGH与ACE、DPP-IV的结合位点进行预测，蛋白ACE(PDB code:1O8A)、DPP-IV(PDB：1NU6)的三维结构来自Protein Data Bank(https://www.rcsb.org/)。多肽和蛋白质之间是否存在相互作用通过结果产生的P值和结合位点表示，P值越小则多肽和蛋白质结合可能性越大，若P值>0.5，理论上多肽和蛋白质没有结合可能性。结合位点表示多肽与蛋白质结合位点，若多肽同蛋白质的活性位点相结合，则可以抑制蛋白质同其他蛋白质之间的性互作用，从而抑制该蛋白质活性。
多肽LLEPIGVVGH同ACE结合的p值为0.001439，结合位点为Trp279,Gln281#,His353#,Ala354#,His383#,Glu384#,His387#,Glu411#,Phe457,Phe460,Lys511#,His513#,Tyr520#,Tyr523#其中带有#标记的为文献中报道的ACE的重要的活性位点和结合位点，表明多肽LLEPIGVVGH具有良好的ACE抑制活性。
多肽LLEPIGVVGH同DPP-IV结合的p值为0.02947，结合位点为Tyr48,Glu206#,Tyr547#,Trp627,Trp629#,Tyr662#,Tyr666#,Tyr752其中带有#标记的为文献中报道的DPP-IV的重要的活性位点和结合位点，表明多肽LLEPIGVVGH具有良好的DPP-IV抑制活性。
本发明具有如下优点：
1.本发明从发酵枸杞蛋白中得到了ACE抑制肽，多肽LLEPIGVVGH具有良好的ACE抑制活性，半抑制浓度(IC50)为215.24μM。为ACE抑制肽提供了更加多样的来源，为ACE抑制肽提供了更多的研究参考。
2.本发明从发酵枸杞蛋白中得到了DPP-IV抑制肽，多肽LLEPIGVVGH具有良好的DPP-IV抑制活性，半抑制浓度(IC50)为208.29μM。为DPP-IV抑制肽提供了更加多样的来源，为DPP-IV抑制肽提供了更多的研究参考。
具体实施方式
实施例1多肽LLEPIGVVGH的鉴定
将枸杞蛋白经过枯草芽孢杆菌发酵、酸沉淀和乙醇沉淀以及LC-MS/MS分析，通过生物信息学和构效关系筛选对于ACE有抑制活性的生物活性肽。
其具体方法如下：
(1)枸杞蛋白提取物的制备
以10g干枸杞为原料，称取枸杞并加入100mL去离子水浸泡2小时后粉碎，超声提取60min，于5000rpm离心10min，9.6g沉淀用于提取枸杞蛋白。
沉淀冷冻干燥后再次粉碎得到枸杞粉，枸杞粉中加入192mL的有机溶剂提取液，正己烷:乙醇＝2.6:1(v/v)，于温度50℃、转速150rpm搅拌提取1小时，过滤，滤饼再用与上述相同的有机溶剂提取液提取一次，提取两次后过滤，滤饼冷冻干燥后为7.5g枸杞蛋白。
(2)枸杞活性肽的制备
将枸杞蛋白加入112mL离子水，用1M的氢氧化钠溶液调节pH至7.5，接种微生物菌种(枯草芽孢杆菌)，菌含量为2*108CFU/mL，于37℃发酵48小时；发酵结束后在13000rpm离心15min，取上清液冷冻干燥，得到1g发酵粗提取物。
发酵粗提取物中加入5mL的0.01M的盐酸，在2℃匀浆8min后，于12000rpm离心20min，取上清液加入3倍体积的无水乙醇，4℃静置24小时，于12000rpm离心20min，取上清冷冻干燥，得到0.383g枸杞多肽。
将枸杞多肽用LTQ Orbitrap Velos进行质谱分析：将枸杞多肽除盐，C18SPE预处理柱，经2mL乙腈活化，再用2mL的0.1％(v/v)TFA溶液洗去乙腈。样品用50％(v/v)TFA溶液调节p H值至2后过柱。经2mL的0.1％(v/v)TFA液脱盐后,用1mL 80％(v/v)乙腈/0.1％(v/v)TFA溶液分3次洗脱,洗脱液冷冻干燥后于-20℃保存,用于质谱分析。将冻干样品加适量0.1％(v/v)甲酸复溶，配制成0.5μg/μL的溶液，使用线性离子阱静电场轨道阱组合质谱仪(LTQ Orbitrap Velos)对样品进行质谱分析，设置离子传输毛细管的温度250℃，电喷雾电压2.2kV，归一化碰撞能量35.0％。均使用数据依赖模式(data-dependent mode)对MS和MS/MS进行图谱采集。质谱扫描条件设定为：从每次m/z＝400～2000的全扫描中选择10个最高丰度离子峰进行MS/MS扫描。样品平行分析三次，取三次分析鉴定到的共同肽段进行统计。将采集的*.raw文件数据用Thermo Proteome Discoverer Daemon(v1.4)转换成*.mgf格式，再用Mascot(version 2.3.0，Matrix Science，London，UK)谱图在茄科植物蛋白库solanaceae.fasta(https://www.uniprot.org/)中进行检索。三次分析共鉴定到来源于14个不同蛋白的75条共同肽段，41.33％的肽段来自蛋白Fibrillin，肽段中氨基酸数量在8～27之间，计算分子质量在920.4491～2742.4664(Da)，表一为部分枸杞多肽的质谱鉴定结果。
表一枸杞多肽的质谱鉴定结果
根据发明内容中关于构效关系的阐述，对鉴定到的共同肽段进行筛选，获得来源于Aldehyde dehydrogenase family 2 member C4蛋白的序列为LLEPIGVVGH的多肽。
实施例2枸杞活性肽LLEPIGVVGH的ACE抑制活性检测
多肽LLEPIGVVGH由南京杰肽生物科技有限公司合成，氨基酸序列为Leu-Leu-Glu-Pro-Ile-Gly-Val-Val-Gly-His，为单链线性结构，白色粉末状，易溶于水，分子量为1033.24Da。
SEQ ID No.1的信息
(a)序列特征
*长度：10氨基酸
*类型：氨基酸
*链型：单链
(b)分子类型：蛋白
序列描述：
SEQ ID No.1
LLEPIGVVGH
N-(3-(2-呋喃酰)丙烯酰-苯氨酰-谷氨酰-谷氨酸(FAPGG，λmax＝340nm，ε＝2270M-1cm-1，分子量399.40)可以被ACE酶解成N-[3-(呋喃)丙稀醇酰]-2-苯丙氨酸(FAP，λmax＝340nm，ε＝1512M-1cm-1)和双甘氨肽(GG，在340nm处无吸收)，因此可以作为ACE的模拟底物。1mM FAPGG完全转化成FAP和GG的吸光值为0.758，因此可根据340nm吸光度的变化值计算抑制率。
反应体系
(1)缓冲溶液：0.1M PBS缓冲液(pH＝8.2，含300mM NaCl)
(2)底物溶液：使用上述缓冲液配制浓度为1.6mM的FAPGG溶液。
(3)酶溶液：使用上述缓冲溶液将ACE配制成0.2U/mL的溶液。
(4)样品溶液：按照实验需要将多肽LLEPIGVVGH用上述缓冲液配制成1.0，0.5，0.1mg/mL浓度的溶液。
实验在96孔板中进行。按照表二依次加入样品溶液、ACE溶液和底物溶液，混合均匀，立即用酶标仪于340nm波长下测定吸光度，记为OD0，37℃温育30min后再次于340nm波长下测定吸光度，记为OD1。测定各个样品的孔的吸光度，令ΔOD＝OD0-OD1。每个样品平行测定3次。
表二ACE抑制活性反应体系
“-”代表加入该列等体积的PBS缓冲液
ACE抑制率计算公式：
I＝[(ΔODControl-ΔODSample)/(ΔODControl-ΔODblank)]*100％
ΔODcontrol表示反应中样品溶液被等量的缓冲液取代后吸光度的变化；ΔODSample表示反应中样品溶液的吸光度变化；而ΔODblank表示反应中样品溶液、酶溶液被等量的缓冲液取代后吸光度的变化
表三ACE抑制活性实验的吸光度
表四不同浓度的LLEPIGVVGH对ACE的抑制活性
按上述方法对不同浓度多肽LLEPIGVVGH进行ACE抑制活性检测。表三为不同浓度LLEPIGVVGH对于ACE抑制活性实验的吸光度，表四为不同浓度的LLEPIGVVGH对ACE的抑制活性，由此计算多肽LLEPIGVVGH半抑制浓度(IC50)为215.24±48.56μM。
实施例3枸杞活性肽LLEPIGVVGH的DPP-IV抑制活性检测
DPP-IV可使胰高血糖素样肽-1(GLP-1)发生降解，是因为GLP-1具有X-Ala结构，对于N端为X-Pro、X-Ala的肽段，DPP-IV可将该二肽选择性切除。本实验中我们选择Gly-Pro-p-nitroanilide代替GLP-1作为DPP-IV的模拟底物，生成的对硝基苯胺在405nm有吸收，可以通过吸光度计算DPP-IV的抑制活性。
反应体系为：
(1)缓冲溶液：100mM的Tris-HCl缓冲液(pH＝8.0)。
(2)底物溶液：使用上述缓冲液配制浓度为1.59mM的Gly-pro-p-nitroanilide溶液。
(3)酶溶液：使用上述缓冲溶液配置0.01U/mL的DPP-IV溶液。
(4)样品溶液：按照实验需要将多肽LLEPIGVVGH用上述缓冲液配制成1.0，0.5，0.1mg/mL浓度的溶液。
(5)终止溶液：1M的醋酸钠缓冲溶液(PH＝4.0)。
实验在96孔板中进行。按照表五加入样品溶液、DPP-IV溶液和底物溶液，混合均匀，37℃温育60min后，加入100μL终止溶液，于405nm波长下测定吸光度，记为OD。测定各个样品的孔的吸光度，每个样品平行测定3次。
表五DPP-IV抑制活性反应体系
“-”代表加入该列等体积的Tris-HCl缓冲液
DPP-IV抑制率计算公式：
I＝[(ODControl-ODSample)/(ODControl-ODblank)]*100％
ODcontrol表示反应中样品溶液被等量的缓冲液取代后的吸光度；ODSample表示反应中样品溶液的吸光度；而ODblank表示反应中样品溶液、酶溶液被等量的缓冲液取代后的吸光度
表六DPP-IV抑制活性实验吸光度
表七不同浓度的LLEPIGVVGH对DPP-IV的抑制活性
按上述方法对不同浓度多肽LLEPIGVVGH进行DPP-IV抑制活性检测，表六为不同浓度LLEPIGVVGH对于DPP-IV抑制活性实验的吸光度，表七为不同浓度的LLEPIGVVGH对DPP-IV的抑制活性，多肽LLEPIGVVGH半抑制浓度(IC50)为208.29±7.91μM。
序列表
<110> 中国科学院大连化学物理研究所
<120> 一种枸杞ACE、DPP-IV 抑制肽及衍生多肽和应用、混合物
<160> 1
<170> SIPOSequenceListing 1.0
<210> 1
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 1
Leu Leu Glu Pro Ile Gly Val Val Gly His
1 5 10
Claims (7)
1.一种枸杞ACE、DPP-IV抑制肽，其特征在于：所述多肽LLEPIGVVGH，具有序列表SEQ IDNO：1中氨基酸序列；该多肽的氨基酸序列具体为Leu-Leu-Glu-Pro-Ile-Gly-Val-Val-Gly-His。
2.一种权利要求1多肽为LLEPIGVVGH的衍生多肽，其中所衍生的多肽为在SEQ ID NO：1所示氨基酸序列经过取代、缺失和/或添加一个或2个以上氨基酸且与权利要求1所述小肽具有相同功能的衍生多肽。
3.一种权利要求1或2所述的肽在制备血管紧张素转换酶(angiotensin-convertingenzyme,ACE)抑制剂和二肽基肽酶(dipeptidyl peptidase IV,DPP-IV)抑制剂和/或降血压、降血糖药物中的应用。
4.按照权利要求3所述的应用，血管紧张素转换酶(angiotensin-converting enzyme,ACE)抑制剂和二肽基肽酶(dipeptidyl peptidase IV,DPP-IV)抑制剂和/或降血压、降血糖药物是以多LLEPIGVVGH为活性成份,其中还可添加药物学上可接受的载体或辅料。
5.一种权利要求1或2所述的多肽作为活性成份在体外血管紧张素转换酶(angiotensin-converting enzyme,ACE)抑制剂中的应用，或作为活性成份在具有降血压的功能性食品中的应用；在体外二肽基肽酶(dipeptidyl peptidase IV,DPP-IV)抑制剂中的应用，或作为活性成份在具有降血糖的功能性食品中的应用。
6.按照权利要求5所述的应用，所述抑制剂或功能性食品中还可添加药物学上可接受的载体或辅料。
7.一种混合物，为血管紧张素转换酶抑制剂、降血压药物或具有降血压的功能性食品，其是以多LLEPIGVVGH为活性成份,其中可添加药物学上可接受的载体或辅料。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910806960.XA CN112442108B (zh) | 2019-08-29 | 2019-08-29 | 一种枸杞ace、dpp-iv抑制肽及衍生多肽和应用、混合物 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910806960.XA CN112442108B (zh) | 2019-08-29 | 2019-08-29 | 一种枸杞ace、dpp-iv抑制肽及衍生多肽和应用、混合物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112442108A true CN112442108A (zh) | 2021-03-05 |
| CN112442108B CN112442108B (zh) | 2021-11-30 |
Family
ID=74740814
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910806960.XA Active CN112442108B (zh) | 2019-08-29 | 2019-08-29 | 一种枸杞ace、dpp-iv抑制肽及衍生多肽和应用、混合物 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112442108B (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113801192A (zh) * | 2021-08-31 | 2021-12-17 | 华南理工大学 | 一种抑制二肽基肽酶iv的四肽及其应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011064402A2 (fr) * | 2009-11-30 | 2011-06-03 | Laboratoires Expanscience | Extrait de graines d'acacia macrostachya et compositions le comprenant |
| CN104561205A (zh) * | 2014-12-27 | 2015-04-29 | 宁夏医科大学 | 一种制备枸杞ace抑制肽的方法 |
| CN106554388A (zh) * | 2015-09-25 | 2017-04-05 | 中国科学院大连化学物理研究所 | 具有ace和dpp-iv抑制活性的多肽及其应用 |
| CN108949886A (zh) * | 2018-08-23 | 2018-12-07 | 王召利 | 一种降血糖植物活性肽及其制备方法 |
-
2019
- 2019-08-29 CN CN201910806960.XA patent/CN112442108B/zh active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011064402A2 (fr) * | 2009-11-30 | 2011-06-03 | Laboratoires Expanscience | Extrait de graines d'acacia macrostachya et compositions le comprenant |
| CN104561205A (zh) * | 2014-12-27 | 2015-04-29 | 宁夏医科大学 | 一种制备枸杞ace抑制肽的方法 |
| CN106554388A (zh) * | 2015-09-25 | 2017-04-05 | 中国科学院大连化学物理研究所 | 具有ace和dpp-iv抑制活性的多肽及其应用 |
| CN108949886A (zh) * | 2018-08-23 | 2018-12-07 | 王召利 | 一种降血糖植物活性肽及其制备方法 |
Non-Patent Citations (3)
| Title |
|---|
| CEREN DASKAYA-DIKMEN ET AL.: ""Angiotensin-I-Converting Enzyme (ACE)-Inhibitory Peptides from Plants"", 《NUTRIENTS》 * |
| 庄晶玲 等: ""利用LC-MS/MS筛选发酵法制备的枸杞生物活性肽"", 《中国食品科学技术学会第十六届年会暨第十届中美食品业高层论坛论文摘要集》 * |
| 范彦娜 等: ""枸杞ACE抑制肽成分提取及测定研究"", 《中国卫生标准管理》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113801192A (zh) * | 2021-08-31 | 2021-12-17 | 华南理工大学 | 一种抑制二肽基肽酶iv的四肽及其应用 |
| CN113801192B (zh) * | 2021-08-31 | 2023-06-20 | 华南理工大学 | 一种抑制二肽基肽酶iv的四肽及其应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112442108B (zh) | 2021-11-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Kohlhoff et al. | Exploring the proteomes of the venoms of the Peruvian pit vipers Bothrops atrox, B. barnetti and B. pictus | |
| CN107163129B (zh) | κ-酪蛋白来源生物活性肽的制备和应用 | |
| Saputri et al. | Inhibition of angiotensin converting enzyme (ACE) activity by some Indonesia edible plants | |
| CN111153963A (zh) | 抗炎五肽及其提取分离方法和在改善记忆中的应用 | |
| Liu et al. | Novel peptides with α-glucosidase inhibitory activity from Changii Radix hydrolysates | |
| Ding et al. | Identification and characterization of dipeptidyl peptidase IV inhibitory peptides from wheat gluten proteins | |
| CN112442108B (zh) | 一种枸杞ace、dpp-iv抑制肽及衍生多肽和应用、混合物 | |
| Deng et al. | Synthesis and pharmacological evaluation of a novel synthetic peptide CWHTH based on the Styela clava-derived natural peptide LWHTH with improved antioxidant, hepatoprotective and angiotensin converting enzyme inhibitory activities | |
| CN112442109B (zh) | 一种枸杞ace抑制肽及衍生多肽和应用、混合物 | |
| CN112442110B (zh) | 一种枸杞ace抑制肽和衍生多肽及应用、混合物 | |
| CN112442111B (zh) | 一种枸杞ace抑制肽和衍生多肽以及应用、混合物 | |
| CN112500449B (zh) | 一种枸杞ace抑制肽以及衍生多肽和应用、混合物 | |
| Bhadkaria et al. | Peptide fraction from moth bean (Vigna aconitifolia (Jacq.)) seed protein hydrolysate demonstrates multifunctional characteristics | |
| CN106554387B (zh) | 具有ace和dpp-iv双重抑制活性的九肽及其应用 | |
| CN112442104B (zh) | 发酵法制备枸杞活性肽及方法和应用与抑制剂、功能食品 | |
| CN112125952B (zh) | 一种猪源ace抑制活性多肽与药物组合物或食品及应用 | |
| CN113801192B (zh) | 一种抑制二肽基肽酶iv的四肽及其应用 | |
| CN117069796A (zh) | 一种用于降低血糖的多肽 | |
| CN110498833B (zh) | 一种具有ace抑制作用的三肽及其应用 | |
| CN110845573B (zh) | 一种多肽及其在制备ace抑制剂或降血压药物中的应用 | |
| CN117126243B (zh) | 一种小分子肽pypdw及其应用 | |
| CN113563420B (zh) | 一种抗氧化活性肽及其应用 | |
| CN109517035B (zh) | 一种西兰花蛋白来源的ace抑制肽、ace抑制肽酶切代谢产物及其制备方法和应用 | |
| CN101144080A (zh) | 重组人VIP-Humanin融合蛋白制备方法 | |
| CN115572321A (zh) | 一种酵母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 |