CN114716524B - 抑制α-淀粉酶和α-葡萄糖苷酶的熟小米醇溶蛋白肽 - Google Patents
抑制α-淀粉酶和α-葡萄糖苷酶的熟小米醇溶蛋白肽 Download PDFInfo
- Publication number
- CN114716524B CN114716524B CN202210396241.7A CN202210396241A CN114716524B CN 114716524 B CN114716524 B CN 114716524B CN 202210396241 A CN202210396241 A CN 202210396241A CN 114716524 B CN114716524 B CN 114716524B
- Authority
- CN
- China
- Prior art keywords
- alpha
- amylase
- glucosidase
- peptide
- ktgsgaegmhggk
- 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
- 102000004139 alpha-Amylases Human genes 0.000 title claims abstract description 46
- 108090000637 alpha-Amylases Proteins 0.000 title claims abstract description 46
- 229940024171 alpha-amylase Drugs 0.000 title claims abstract description 46
- 102100024295 Maltase-glucoamylase Human genes 0.000 title claims abstract description 45
- 108010028144 alpha-Glucosidases Proteins 0.000 title claims abstract description 45
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 44
- 244000062793 Sorghum vulgare Species 0.000 title claims abstract description 30
- 235000019713 millet Nutrition 0.000 title claims abstract description 30
- 108060006613 prolamin Proteins 0.000 title claims abstract description 20
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 9
- 102000004196 processed proteins & peptides Human genes 0.000 title abstract description 20
- 235000013305 food Nutrition 0.000 claims abstract description 7
- 206010012601 diabetes mellitus Diseases 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 7
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 7
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 4
- 239000003392 amylase inhibitor Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 230000036541 health Effects 0.000 claims description 3
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 claims description 2
- 239000003888 alpha glucosidase inhibitor Substances 0.000 claims description 2
- 239000002417 nutraceutical Substances 0.000 claims description 2
- 235000021436 nutraceutical agent Nutrition 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 15
- 238000012216 screening Methods 0.000 abstract description 10
- 238000000034 method Methods 0.000 abstract description 7
- 239000003472 antidiabetic agent Substances 0.000 abstract description 3
- 231100000252 nontoxic Toxicity 0.000 abstract 1
- 230000003000 nontoxic effect Effects 0.000 abstract 1
- 230000003993 interaction Effects 0.000 description 21
- 108010033276 Peptide Fragments Proteins 0.000 description 16
- 102000007079 Peptide Fragments Human genes 0.000 description 16
- 238000003032 molecular docking Methods 0.000 description 16
- 230000002209 hydrophobic effect Effects 0.000 description 15
- 229910052739 hydrogen Inorganic materials 0.000 description 13
- 239000001257 hydrogen Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 238000000338 in vitro Methods 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 230000029087 digestion Effects 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 238000000108 ultra-filtration Methods 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 241000024188 Andala Species 0.000 description 3
- 108010019160 Pancreatin Proteins 0.000 description 3
- 108010009736 Protein Hydrolysates Proteins 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 230000031891 intestinal absorption Effects 0.000 description 3
- 229940055695 pancreatin Drugs 0.000 description 3
- 239000003531 protein hydrolysate Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 230000035495 ADMET Effects 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 102000057297 Pepsin A Human genes 0.000 description 2
- 108090000284 Pepsin A Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 231100000460 acute oral toxicity Toxicity 0.000 description 2
- 238000010535 acyclic diene metathesis reaction Methods 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000001079 digestive effect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
- 239000000413 hydrolysate Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229940111202 pepsin Drugs 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000012064 sodium phosphate buffer Substances 0.000 description 2
- 238000003041 virtual screening Methods 0.000 description 2
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- DQJCDTNMLBYVAY-ZXXIYAEKSA-N (2S,5R,10R,13R)-16-{[(2R,3S,4R,5R)-3-{[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-(ethylamino)-6-hydroxy-2-(hydroxymethyl)oxan-4-yl]oxy}-5-(4-aminobutyl)-10-carbamoyl-2,13-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazaheptadecan-1-oic acid Chemical compound NCCCC[C@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@@H](C)NC(=O)C(C)O[C@@H]1[C@@H](NCC)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DQJCDTNMLBYVAY-ZXXIYAEKSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- IFBHRQDFSNCLOZ-IIRVCBMXSA-N 4-nitrophenyl-α-d-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC1=CC=C([N+]([O-])=O)C=C1 IFBHRQDFSNCLOZ-IIRVCBMXSA-N 0.000 description 1
- VWEWCZSUWOEEFM-WDSKDSINSA-N Ala-Gly-Ala-Gly Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(O)=O VWEWCZSUWOEEFM-WDSKDSINSA-N 0.000 description 1
- MNZHHDPWDWQJCQ-YUMQZZPRSA-N Ala-Leu-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O MNZHHDPWDWQJCQ-YUMQZZPRSA-N 0.000 description 1
- ZBLQIYPCUWZSRZ-QEJZJMRPSA-N Ala-Phe-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CC1=CC=CC=C1 ZBLQIYPCUWZSRZ-QEJZJMRPSA-N 0.000 description 1
- YFHATWYGAAXQCF-JYJNAYRXSA-N Arg-Pro-Phe Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 YFHATWYGAAXQCF-JYJNAYRXSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- PKVWNYGXMNWJSI-CIUDSAMLSA-N Gln-Gln-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O PKVWNYGXMNWJSI-CIUDSAMLSA-N 0.000 description 1
- KVXVVDFOZNYYKZ-DCAQKATOSA-N Gln-Gln-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O KVXVVDFOZNYYKZ-DCAQKATOSA-N 0.000 description 1
- VSXBYIJUAXPAAL-WDSKDSINSA-N Gln-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CCC(N)=O VSXBYIJUAXPAAL-WDSKDSINSA-N 0.000 description 1
- XFAUJGNLHIGXET-AVGNSLFASA-N Gln-Leu-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O XFAUJGNLHIGXET-AVGNSLFASA-N 0.000 description 1
- VOORMNJKNBGYGK-YUMQZZPRSA-N Glu-Gly-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)N VOORMNJKNBGYGK-YUMQZZPRSA-N 0.000 description 1
- KKBWDNZXYLGJEY-UHFFFAOYSA-N Gly-Arg-Pro Natural products NCC(=O)NC(CCNC(=N)N)C(=O)N1CCCC1C(=O)O KKBWDNZXYLGJEY-UHFFFAOYSA-N 0.000 description 1
- IRJWAYCXIYUHQE-WHFBIAKZSA-N Gly-Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)CN IRJWAYCXIYUHQE-WHFBIAKZSA-N 0.000 description 1
- 102000002068 Glycopeptides Human genes 0.000 description 1
- 108010015899 Glycopeptides Proteins 0.000 description 1
- FDQYIRHBVVUTJF-ZETCQYMHSA-N His-Gly-Gly Chemical compound [O-]C(=O)CNC(=O)CNC(=O)[C@@H]([NH3+])CC1=CN=CN1 FDQYIRHBVVUTJF-ZETCQYMHSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 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 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
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- BTSXLXFPMZXVPR-DLOVCJGASA-N Lys-Ala-His Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCCCN)N BTSXLXFPMZXVPR-DLOVCJGASA-N 0.000 description 1
- JHNOXVASMSXSNB-WEDXCCLWSA-N Lys-Thr-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O JHNOXVASMSXSNB-WEDXCCLWSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 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
- BBDSZDHUCPSYAC-QEJZJMRPSA-N Phe-Ala-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O BBDSZDHUCPSYAC-QEJZJMRPSA-N 0.000 description 1
- ZPPVJIJMIKTERM-YUMQZZPRSA-N Pro-Gln-Gly Chemical compound OC(=O)CNC(=O)[C@H](CCC(=O)N)NC(=O)[C@@H]1CCCN1 ZPPVJIJMIKTERM-YUMQZZPRSA-N 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- UQFYNFTYDHUIMI-WHFBIAKZSA-N Ser-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CO UQFYNFTYDHUIMI-WHFBIAKZSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000004531 blood pressure lowering effect Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000021245 dietary protein Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 206010016766 flatulence Diseases 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000003517 fume Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 1
- 108010050848 glycylleucine Proteins 0.000 description 1
- 108010015792 glycyllysine Proteins 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 238000005040 ion trap Methods 0.000 description 1
- 108010000761 leucylarginine Proteins 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- 229960001110 miglitol Drugs 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 229960001729 voglibose Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 108010027345 wheylin-1 peptide Proteins 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
- C07K14/415—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
-
- 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
- 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
- A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/06—Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/62—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode
- G01N27/626—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode using heat to ionise a gas
-
- 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
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Health & Medical Sciences (AREA)
- Polymers & Plastics (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Botany (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Pediatric Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Electrochemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
Abstract
本申请提供了抑制α‑淀粉酶和α‑葡萄糖苷酶的熟小米醇溶蛋白肽及其应用和筛选方法,其序列选自SEQ ID NO.1‑6。本申请的肽能够同时有效抑制α‑葡萄糖苷酶和α‑淀粉酶活性,且安全无毒无副作用,因此作为功能成分用于食品、保健品以及降糖药品中,具有良好的潜力和应用前景。
Description
技术领域
本申请属于蛋白领域,具体地,本申请提供了多个抑制α-淀粉酶和α-葡萄糖苷酶的熟小米醇溶蛋白肽及其应用和筛选方法。
背景技术
糖尿病已经成为一种全球流行的代谢疾病,主要表现为血糖水平升高引起的机体脂肪、碳水化合物和蛋白质代谢紊乱。近年来,糖尿病患病率一直在稳步增长。非胰岛素依赖型糖尿病即2型糖尿病常见发生于各个年龄段的人群中,目前90%的糖尿病患者已被诊断为2型糖尿病。膳食淀粉可以被α-淀粉酶消化成大量的麦芽糖,然后再被α-葡萄糖苷酶消化为葡萄糖。淀粉快速降解为葡萄糖导致的血糖水平升高被称为餐后高血糖症,这是2型糖尿病的重要指标。因此可以通过抑制α-淀粉酶和α-葡萄糖苷酶,延迟碳水化合物水解为葡萄糖的速率来实现控制餐后血糖的目的。目前用于治疗2型糖尿病的市售药物,例如二甲双胍,阿卡波糖、伏格列波糖和米格列酮可以抑制α-淀粉酶和α-葡萄糖苷酶活性,但摄入这些降血糖药物也会带来一些副作用,例如胀气和腹泻等。
近年来,许多食源性肽已被证明具有抗菌特性、降血压作用、降低胆固醇、抗血栓形成和抗氧化活性等。食物蛋白质作为功能肽的主要来源受到了广泛关注。小米醇溶蛋白已被证实具有较好的改善血糖代谢的功能,也就是说小米醇溶蛋白在通过灌胃被给予糖尿病小鼠后,经过胃肠道消化被水解为氨基酸和肽,进入血液循环发挥包括降糖等生理作用。目前已从小米蛋白中分离出了抗氧化、抗炎以及脂肪酶抑制肽,但尚未有关于小米蛋白降糖肽的相关研究。因此,有必要探究小米醇溶蛋白水解得到的小分子肽中可以作为潜在的功能性降糖物质的肽段。
发明内容
针对以上问题,一方面,本申请提供抑制α-淀粉酶和α-葡萄糖苷酶的熟小米醇溶蛋白肽,所述肽的序列选自SEQ ID NO.1-6。
进一步地,所述肽的序列为SEQ ID NO.1或SEQ ID NO.2。
另一方面,本申请提供了组合物,所述组合物包含上述肽以及药学、食品或保健品上可接受的辅料。
另一方面,本申请提供了上述肽或者组合物在制备α-淀粉酶和/或α-葡萄糖苷酶抑制剂中的用途。
另一方面,本申请提供了上述肽或者组合物在制备治疗糖尿病的药物中的应用。
另一方面,本申请提供了上述肽或者组合物在制备适用于糖尿病人群的降糖食品或保健品中的应用。
进一步地,所述糖尿病为2型糖尿病。
另一方面,本申请提供了筛选上述肽的方法,所述方法包括:
(1)体外模拟消化:使用酶法对熟小米醇溶蛋白进行水解以得到蛋白水解物;
(2)筛选:对蛋白水解物进行超滤处理;通过质谱得到超滤级分中置信度较高的肽段序列;采用殷赋云平台对得到的肽段序列进行虚拟筛选,根据肽段的格点打分以及内部排斥能;筛选得到分别与α-葡萄糖苷酶和α-淀粉酶对接效果较好的肽段;比对分别与α-葡萄糖苷酶和α-淀粉酶对接效果较好的肽段,得到同时能与α-葡萄糖苷酶和α-淀粉酶有较好对接效果的肽段;
(3)活性位点分析及体外功能预测:使用殷赋云平台对筛选得到的肽序列分别与α-淀粉酶和α-葡萄糖苷酶进行对接,确定其与α-淀粉酶和α-葡萄糖苷酶作用的关键氨基酸及相互作用力;然后对筛选得到的同时能与α-葡萄糖苷酶和α-淀粉酶有较好对接效果的肽序列进行水溶性、不稳定性、等电点、半衰期和ADMET性质的预测。
进一步地,所述水解使用胃蛋白酶和胰酶。
进一步地,所述超滤级分为<3kDa的级分。
有益效果:
本次首次从熟小米醇溶蛋白中筛选得到了能够同时有效抑制α-葡萄糖苷酶和α-淀粉酶活性的6条未经报道的小肽QQLRPF、AGAGPQGRP、FALQGAAFLGSA、QQQQLLR、KTGSGAEGMHGGK和KAHAALGAK,并明确了小肽QQLRPF、AGAGPQGRP、FALQGAAFLGSA、QQQQLLR、KTGSGAEGMHGGK和KAHAALGAK的结构;同时QQLRPF、AGAGPQGRP、FALQGAAFLGSA、QQQQLLR、KTGSGAEGMHGGK和KAHAALGAK具有安全无毒无副作用的优点,因此作为功能成分用于食品、保健品以及降糖药品中,具有良好的潜力和应用前景。
附图说明
图1为QQLRPF与α-葡萄糖苷酶和α-淀粉酶对接结果图。
图2为AGAGPQGRP与α-葡萄糖苷酶和α-淀粉酶对接结果图;
图3为FALQGAAFLGSA与α-葡萄糖苷酶和α-淀粉酶对接结果图;
图4为QQQQLLR与α-葡萄糖苷酶和α-淀粉酶对接结果图;
图5为KTGSGAEGMHGGK与α-葡萄糖苷酶和α-淀粉酶对接结果图;
图6为KAHAALGAK与α-葡萄糖苷酶和α-淀粉酶对接结果图;
图7为QQLRPF、AGAGPQGRP、FALQGAAFLGSA、QQQQLLR、KTGSGAEGMHGGK和KAHAALGAK的α-葡萄糖苷酶抑制率图;
图8为QQLRPF、AGAGPQGRP、FALQGAAFLGSA、QQQQLLR、KTGSGAEGMHGGK和KAHAALGAK的α-淀粉酶抑制率图。
具体实施方式
实施例1熟小米醇溶蛋白的提取
首先将小米磨成粉,并通过60目筛。然后将小米粉以1:5(w/v)的比例分散在正己烷中,37℃水浴振荡4h后静置,待小米粉和正己烷明显分层后,倒去上层正己烷并收集下层沉淀物,在通风橱中干燥24h以完全除去正己烷,所得的小米粉即为生小米粉。将脱脂生小米粉与蒸馏水按1:5的比例混合均匀,在沸水浴中糊化10min后,将沉淀物在烘箱43℃下干燥24h,然后打粉并通过60目筛网过筛即可得到熟小米粉。将熟小米粉以1:7(m/v)的比例分散在70%乙醇溶液中,然后设置温度为40℃,在水浴振荡器中振荡2h。之后将上述反应溶液在7000rpm下离心10min,并收集上清液,用透析袋透析24h。透析过程中更换蒸馏水4次。透析结束后将透析液在7000rpm下离心5min,收集沉淀,冻干后得到熟小米醇溶蛋白,蛋白含量为85%。
实施例2熟小米醇溶蛋白的体外模拟消化
将熟小米醇溶蛋白样品与蒸馏水以1:5的比例混合,调节pH至3,加入2000U/mL的胃蛋白酶,反应2h后调节pH到7,再加入胰酶使得消化液中胰酶活力为100U胰蛋白酶/mL消化液,继续反应2h,反应结束后沸水浴灭酶10min以终止反应。最后在7000rpm下离心10min收集沉淀,得到蛋白消化后的水解产物。
实施例3熟小米醇溶蛋白体外模拟消化产物的超滤
首先用超纯水预清洗Ultra-15离心过滤器,洗后甩干。然后选取分离分子量为3kDa的离心过滤器,向过滤器内加入不超过15mL的样本,将盖好盖子的过滤装置放入离心转子中,转速为5000×g,旋转约30min。离心结束后,取下盖子和过滤器,将离心管中的液体收集并冻干,即为小于3kDa的蛋白水解物超滤样本。
实施例4熟小米醇溶蛋白体外模拟消化产物的质谱测序及筛选
采用电喷雾-组合型离子阱Orbitrap质谱仪对小于3kDa的水解物组分进行质谱测序,采用De novo的方法进行多肽序列解析,得到所有置信度较高的肽序列。然后基于格点打分小于-115kcal/mol和内部排斥能小于30kcal/mol对测序得到的肽段分别与α-葡萄糖苷酶和α-淀粉酶进行虚拟筛选,筛选结果如表1和表2所示。对比表1和表2可以找出,小肽QQLRPF、AGAGPQGRP、FALQGAAFLGSA、QQQQLLR、KTGSGAEGMHGGK和KAHAALGAK同时跟α-葡萄糖苷酶和α-淀粉酶具有较好的对接效果。
表1虚拟筛选中与α-淀粉酶对接效果较好的肽段
表2虚拟筛选中与α-葡萄糖苷酶对接效果较好的肽段
实施例5小米醇溶蛋白中筛选得到降糖肽的分子对接及体外功能预测
继续使用殷赋云平台中的蛋白/核酸/多肽小分子对接Dock 6.9软件进一步进行精确分子对接分析,找出QQLRPF、AGAGPQGRP、FALQGAAFLGSA、QQQQLLR、KTGSGAEGMHGGK和KAHAALGAK与α-葡萄糖苷酶和α-淀粉酶作用的活性位点。如图1A-B所示,分析QQLRPF与α-淀粉酶的相互作用力发现,QQLRPF与α-淀粉酶的残基Trp 59、Leu 165、Trp 58、Try 62、Ile235和His 305形成了疏水相互作用。除此之外,残基His 305以及Gln 63与QQLRPF之间形成了氢键。肽段QQLRPF还分别与α-淀粉酶的残基Glu 233和His 101之间形成了盐桥,也就是离子键。分析QQLRPF与α-葡萄糖苷酶的相互作用力发现,QQLRPF与α-葡萄糖苷酶的残基Trp481、Ala 555、Trp 516、Trp 376、Leu 677、Leu 678、Leu 650、Phe 297、Val 334、Ala 343和Thr 339形成疏水相互作用,与Thr 339、Arg 429、Glu 427、Gly 399、Asn 301、Gly 651和Ser 676形成氢键,与Asp 282、Asp 616和Glu 377形成盐桥,与Phe 649形成π-π堆积(图1C-D)。如图2A-B所示,AGAGPQGRP与α-淀粉酶的残基Arg 195、His 299和Asp 356形成盐桥,与残基Leu 237、Glu 233和His 201形成氢键,与Tyr 62、Trp 58、Ile 235和Leu 165形成疏水相互作用。此外,AGAGPQGRP与α-葡萄糖苷酶的残基His 105形成盐桥,与Tyr 65和Phe 166形成疏水相互作用,与Lys 225和Gly 228形成氢键(图2C-D)。如图3A-B所示,FALQGAAFLGSA与α-淀粉酶的残基Tyr 151、Leu 165、Tyr 62、Trp 58、Trp 59和Ile 51形成疏水相互作用,与Lys 200形成盐桥,与His 305、Asp 300、Thr 163、Tyr 52和Gln 63形成氢键,与Trp 357形成π-阳离子相互作用,与Tyr 62形成π-π堆积。分析FALQGAAFLGSA与α-葡萄糖苷酶的相互作用力可知,FALQGAAFLGSA与α-葡萄糖苷酶的残基Thr 203、Phe 166、Phe 147、Lys 398、Val 335和Glu 377形成疏水相互作用,与Glu 271和His 304形成盐桥,与Gly 228和Ala348形成氢键(图3C-D)。如图4A-B所示,QQQQLLR与α-淀粉酶的残基Asp 353、Asp 356、Gly304、His 299和Glu 233形成氢键,与His 305、Asp 197和Glu 233形成盐桥,与His 305、Ala198、Trp 58和Tyr 62形成疏水相互作用,与Tyr 62形成π-阳离子相互作用。此外,QQQQLLR与α-葡萄糖苷酶的残基Asp 62、Gly 228、His 332和Gly 399形成氢键,与Asp 202、Asp 333和Glu 271形成盐桥,与Phe 166、Tyr 389、Arg 400、Val 334、Phe 297、Phe 397和Glu 231形成疏水相互作用(图4C-D)。接下来首先对α-淀粉酶与肽段KTGSGAEGMHGGK结合作用力进行分析,如图5A-B所示。肽段KTGSGAEGMHGGK与α-淀粉酶残基Trp 284和Tyr62形成了疏水作用。此外,α-淀粉酶残基Lys 200、Lys 225、Lys 261、Gly 283均与KTGSGAEGMHGGK之间以氢键相连接。除疏水相互作用和氢键外,残基His 201与肽段KTGSGAEGMHGGK之间形成了π-π堆积,而残基Trp284则以π-阳离子相互作用与肽段KTGSGAEGMHGGK连接。此外,His 101、Glu233和Glu 272均与肽段KTGSGAEGMHGGK形成了盐桥,也就是离子键。如图5C-D所示,KTGSGAEGMHGGK与α-葡萄糖苷酶的残基Trp 237和Lys 221形成了疏水相互作用。此外,α-葡萄糖苷酶的残基Gly 399、Lys 225和Ala 343均与KTGSGAEGMHGGK之间以氢键相连接。除疏水相互作用和氢键外,肽段KTGSGAEGMHGGK还与α-葡萄糖苷酶的残基Arg 429形成盐桥,也就是离子键。最后对肽段KAHAALGAK与α-淀粉酶结合后的作用力进行分析,如图6A-B所示。肽段KAHAALGAK与α-淀粉酶残基Leu 235、Ala 198、Leu 165、Tyr 62、Ile 51、Trp 59之间形成了疏水作用,与残基Gln 63、Thr 163之间形成了2个氢键,与残基Glu 240形成了盐桥(离子键),与残基His 201以π-π堆积作用力相连接。然后对肽段KAHAALGAK与α-葡萄糖苷酶结合后的作用力进行分析,如图6C-D所示,KAHAALGAK与α-葡萄糖苷酶残基Glu 377、Thr 339、Val 334、Val 335、Phe 397和Ala 224之间形成疏水相互作用,与残基Arg 429、Asn 301、Lys 225和Gly 222之间形成了4个氢键,与残基Asp 379形成了盐桥。QQLRPF、AGAGPQGRP、FALQGAAFLGSA、QQQQLLR、KTGSGAEGMHGGK和KAHAALGAK的稳定性通过EXPASY平台(http://web.expasy.org/protparam/)评估。利用admetSAR预测QQLRPF、AGAGPQGRP、FALQGAAFLGSA、QQQQLLR、KTGSGAEGMHGGK和KAHAALGAK的ADMET(http://lmmd.ecust.edu.cn/admetsar1/predict/)性质,主要包括人体肠道吸收(Human intestinal absorption,HIA)和急性口服毒性(Acute Oral Toxicity),结果如表3所示。可以看到,六条小肽均具有低毒性,且KTGSGAEGMHGGK、KAHAALGAK和FALQGAAFLGSA三条肽段具有良好的体外稳定性,而QQLRPF、KTGSGAEGMHGGK和KAHAALGAK则具有良好的人体肠道吸收特性。此外,除FALQGAAFLGSA具有疏水特性且呈酸性外,QQLRPF、AGAGPQGRP、QQQQLLR、KTGSGAEGMHGGK和KAHAALGAK均具有较好的亲水性且呈碱性,并且AGAGPQGRP的半衰期也较长。
表3肽段QQLRPF、AGAGPQGRP、FALQGAAFLGSA、QQQQLLR、KTGSGAEGMHGGK和KAHAALGAK的体外功能预测分析
实施例6小米醇溶蛋白中筛选得到肽段的体外α-淀粉酶和α-葡萄糖苷酶抑制活性测定
α-淀粉酶活性测定方法如下所示:500μL样品(0.5%)和500μL 0.02mol/L磷酸钠缓冲液(pH=6.9,0.006mol/L NaCl,包括α-淀粉酶溶液(13U/mL))在25℃下孵育10min,预孵育后加入500μL 1%可溶性淀粉溶液(0.02mol/L磷酸钠缓冲液,pH=6.9,0.006mol/LNaCl),在25℃下孵育10min,并加入1.0mL DNS试剂,之后将上述溶液在沸水浴中煮沸5min,停止反应并冷却到室温。反应液用10mL蒸馏水稀释并在540nm处读数。对照选用去离子水替换样品。计算公式如下:
α-葡萄糖苷酶活性测定方法如下所示:首先配置浓度为1.505mg/mL的底物PNPG溶液(5mmol/L,溶于pH=6.8的0.1mol/L磷酸缓冲液),然后是浓度为0.2mol/L的Na2CO3溶液,最后是α-葡萄糖苷酶溶液(0.8U/ml,溶于pH=6.8的0.1mol/L磷酸缓冲液)。溶液配置结束后,设置以下两组进行测定:
按照上表添加后,37℃下水浴振荡10min,然后加入100μL酶液,继续在37℃下水浴振荡10min,最后加入50μL Na2CO3溶液,并在405nm处测定吸光度值。α-葡萄糖苷酶抑制率的计算公式如下:
结果如图7所示,可以看到QQLRPF和AGAGPQGRP的α-葡萄糖苷酶抑制率显著高于KTGSGAEGMHGGK、KAHAALGAK、FALQGAAFLGSA和QQQQLLR,分别为32.67%和31.57%。FALQGAAFLGSA的α-葡萄糖苷酶抑制率为17.67%,显著高于KTGSGAEGMHGGK(15.64%)、KAHAALGAK(13.77%)和QQQQLLR(15.94%),KAHAALGAK抑制率最低。如图8所示,可以看到QQLRPF的α-淀粉酶抑制率最高,为42.67%,其次为AGAGPQGRP,即37.67%,然后是FALQGAAFLGSA,为24.42%。最后是KTGSGAEGMHGGK、KAHAALGAK和QQQQLLR,分别为15.66%、15.42%和16.99%。
SEQUENCE LISTING
<110> 中国农业大学
<120> 抑制α-淀粉酶和α-葡萄糖苷酶的熟小米醇溶蛋白肽
<160> 6
<170> PatentIn version 3.5
<210> 1
<211> 6
<212> PRT
<213> artificial
<400> 1
Gln Gln Leu Arg Pro Phe
1 5
<210> 2
<211> 9
<212> PRT
<213> artificial
<400> 2
Ala Gly Ala Gly Pro Gln Gly Arg Pro
1 5
<210> 3
<211> 12
<212> PRT
<213> artificial
<400> 3
Phe Ala Leu Gln Gly Ala Ala Phe Leu Gly Ser Ala
1 5 10
<210> 4
<211> 7
<212> PRT
<213> artificial
<400> 4
Gln Gln Gln Gln Leu Leu Arg
1 5
<210> 5
<211> 13
<212> PRT
<213> artificial
<400> 5
Lys Thr Gly Ser Gly Ala Glu Gly Met His Gly Gly Lys
1 5 10
<210> 6
<211> 9
<212> PRT
<213> artificial
<400> 6
Lys Ala His Ala Ala Leu Gly Ala Lys
1 5
Claims (7)
1.抑制α-淀粉酶和α-葡萄糖苷酶的熟小米醇溶蛋白肽,其特征在于,所述肽的序列选自SEQ ID NO.1-6。
2. 根据权利要求1所述的肽,其中所述肽的序列为SEQ ID NO.1或SEQ ID NO.2。
3.组合物,其特征在于,所述组合物包含根据权利要求1或2所述的肽,以及药学、食品或保健品上可接受的辅料。
4.根据权利要求1或2所述的肽在制备α-淀粉酶和/或α-葡萄糖苷酶抑制剂中的用途。
5.根据权利要求1或2所述的肽在制备治疗糖尿病的药物中的应用。
6.根据权利要求1或2所述的肽在制备适用于糖尿病人群的降糖食品或保健品中的应用。
7.根据权利要求5或6所述的应用,其中所述糖尿病为2型糖尿病。
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210396241.7A CN114716524B (zh) | 2022-04-15 | 2022-04-15 | 抑制α-淀粉酶和α-葡萄糖苷酶的熟小米醇溶蛋白肽 |
US18/116,331 US11976098B2 (en) | 2022-04-15 | 2023-03-02 | Cooked millet prolamin peptide for inhibiting alpha-amylase and alpha-glucosidase |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210396241.7A CN114716524B (zh) | 2022-04-15 | 2022-04-15 | 抑制α-淀粉酶和α-葡萄糖苷酶的熟小米醇溶蛋白肽 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114716524A CN114716524A (zh) | 2022-07-08 |
CN114716524B true CN114716524B (zh) | 2023-05-23 |
Family
ID=82242858
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210396241.7A Active CN114716524B (zh) | 2022-04-15 | 2022-04-15 | 抑制α-淀粉酶和α-葡萄糖苷酶的熟小米醇溶蛋白肽 |
Country Status (2)
Country | Link |
---|---|
US (1) | US11976098B2 (zh) |
CN (1) | CN114716524B (zh) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114716524B (zh) | 2022-04-15 | 2023-05-23 | 中国农业大学 | 抑制α-淀粉酶和α-葡萄糖苷酶的熟小米醇溶蛋白肽 |
CN117402215B (zh) * | 2023-12-13 | 2024-02-27 | 黑龙江八一农垦大学 | 抑制α-葡萄糖苷酶活性的玉米肽及其制备方法与应用 |
CN117802697B (zh) * | 2024-03-01 | 2024-05-28 | 中国农业大学 | 一种提升玉米醇溶蛋白纳米纤维膜机械强度的方法 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109021079A (zh) * | 2018-08-31 | 2018-12-18 | 华南理工大学 | 一种降血糖十六肽 |
CN109021075A (zh) * | 2018-08-31 | 2018-12-18 | 华南理工大学 | 一种降血糖十肽 |
CN110183517A (zh) * | 2019-05-31 | 2019-08-30 | 华南理工大学 | 一种降血糖十一肽 |
CN113336825A (zh) * | 2021-07-20 | 2021-09-03 | 浙江农林大学 | 一种具有α-葡萄糖苷酶和α-淀粉酶抑制活性的六肽及其应用 |
CN113801193A (zh) * | 2021-09-16 | 2021-12-17 | 北京工商大学 | 具有α-葡萄糖苷酶抑制活性的麦胚蛋白多肽及其制备 |
CN114106128A (zh) * | 2021-12-06 | 2022-03-01 | 中国农业大学 | 具有α-淀粉酶抑制活性的小米醇溶蛋白肽 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040142325A1 (en) * | 2001-09-14 | 2004-07-22 | Liat Mintz | Methods and systems for annotating biomolecular sequences |
FR3017536B1 (fr) | 2014-02-18 | 2017-05-26 | Univ La Rochelle | Compositions pour la prevention et/ou le traitement de pathologies liees a l'alpha-glucosidase |
WO2020072700A1 (en) * | 2018-10-02 | 2020-04-09 | Dana-Farber Cancer Institute, Inc. | Hla single allele lines |
CN111154823A (zh) | 2020-01-13 | 2020-05-15 | 山西原生肽科技有限公司 | 一种小米活性肽及其制备方法和应用 |
CN113025678A (zh) | 2021-04-22 | 2021-06-25 | 昆明理工大学 | 一种筛选抑制α-淀粉酶活性降血糖肽的方法 |
CN114716524B (zh) | 2022-04-15 | 2023-05-23 | 中国农业大学 | 抑制α-淀粉酶和α-葡萄糖苷酶的熟小米醇溶蛋白肽 |
CN114716523B (zh) | 2022-04-15 | 2023-05-23 | 中国农业大学 | 具有α-葡萄糖苷酶抑制活性的小米醇溶蛋白肽 |
-
2022
- 2022-04-15 CN CN202210396241.7A patent/CN114716524B/zh active Active
-
2023
- 2023-03-02 US US18/116,331 patent/US11976098B2/en active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109021079A (zh) * | 2018-08-31 | 2018-12-18 | 华南理工大学 | 一种降血糖十六肽 |
CN109021075A (zh) * | 2018-08-31 | 2018-12-18 | 华南理工大学 | 一种降血糖十肽 |
CN110183517A (zh) * | 2019-05-31 | 2019-08-30 | 华南理工大学 | 一种降血糖十一肽 |
CN113336825A (zh) * | 2021-07-20 | 2021-09-03 | 浙江农林大学 | 一种具有α-葡萄糖苷酶和α-淀粉酶抑制活性的六肽及其应用 |
CN113801193A (zh) * | 2021-09-16 | 2021-12-17 | 北京工商大学 | 具有α-葡萄糖苷酶抑制活性的麦胚蛋白多肽及其制备 |
CN114106128A (zh) * | 2021-12-06 | 2022-03-01 | 中国农业大学 | 具有α-淀粉酶抑制活性的小米醇溶蛋白肽 |
Also Published As
Publication number | Publication date |
---|---|
US20230331791A1 (en) | 2023-10-19 |
CN114716524A (zh) | 2022-07-08 |
US11976098B2 (en) | 2024-05-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN114716524B (zh) | 抑制α-淀粉酶和α-葡萄糖苷酶的熟小米醇溶蛋白肽 | |
AU666531B2 (en) | Processes for the preparation of amylase inhibitor | |
CN114805483B (zh) | 五种来源于红小豆蛋白的胰脂肪酶抑制剂及其应用 | |
JPS6234396B2 (zh) | ||
CN114106128B (zh) | 具有α-淀粉酶抑制活性的小米醇溶蛋白肽 | |
Mousavi et al. | Antidiabetic bio-peptides of soft and hard wheat glutens | |
JP4711272B2 (ja) | アンジオテンシン変換酵素阻害物質 | |
CN114716523B (zh) | 具有α-葡萄糖苷酶抑制活性的小米醇溶蛋白肽 | |
CN107828842B (zh) | 一种具有抗氧化和dpp-iv抑制功能的核桃蛋白肽 | |
CN115806589B (zh) | 两种小米源寡肽及其在治疗代谢综合征中的应用 | |
CN115960165B (zh) | 一种来源于辣木叶的富硒ace抑制肽及其应用 | |
CN115925854A (zh) | 两种抑制胰脂肪酶和胆固醇酯酶活性的小米醇溶蛋白肽 | |
CN104961805A (zh) | 一种蚕丝蛋白多肽及其制备和应用 | |
JPS61171431A (ja) | アミラ−ゼ阻害物質およびその製造法 | |
CN1379088A (zh) | 萝卜几丁质结合蛋白及其制备方法 | |
JPH09194390A (ja) | 内臓脂肪蓄積抑制剤 | |
CN113563420B (zh) | 一种抗氧化活性肽及其应用 | |
CN112176015B (zh) | 一种海参活性肽高效仿生制备方法 | |
CN117843718B (zh) | 一种蛋源双功能生物活性肽及其制备方法和应用 | |
CN116789742A (zh) | 一种天然高活性降压肽及其制备方法和应用 | |
CN116789741A (zh) | 一种红毛藻源ace抑制肽l1及其制备方法和应用 | |
CN113444145B (zh) | 一种聚球藻血管紧张素转化酶抑制肽及其制备方法与应用 | |
CN117106020B (zh) | 具有消化酶抑制活性的红小豆来源的寡肽及其应用 | |
CN116789743A (zh) | 一种红毛藻源活性肽及其制备方法和应用 | |
CN115838400A (zh) | 两种靶向预防或治疗代谢综合征的红小豆肽 |
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 |