NO333437B1 - Fremgangsmate for a isolere et intestinalt kolesterolbindende protein, sammensetning samt anvendelse av sammensetningen - Google Patents
Fremgangsmate for a isolere et intestinalt kolesterolbindende protein, sammensetning samt anvendelse av sammensetningen Download PDFInfo
- Publication number
- NO333437B1 NO333437B1 NO20051169A NO20051169A NO333437B1 NO 333437 B1 NO333437 B1 NO 333437B1 NO 20051169 A NO20051169 A NO 20051169A NO 20051169 A NO20051169 A NO 20051169A NO 333437 B1 NO333437 B1 NO 333437B1
- Authority
- NO
- Norway
- Prior art keywords
- cholesterol
- protein
- compound
- kda
- biological material
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 35
- 239000000203 mixture Substances 0.000 title claims description 10
- 102000049842 cholesterol binding protein Human genes 0.000 title claims description 4
- 108010011793 cholesterol binding protein Proteins 0.000 title claims description 4
- 230000000968 intestinal effect Effects 0.000 title abstract description 37
- 230000008569 process Effects 0.000 title description 3
- 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 claims abstract description 105
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 102
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 102
- 235000012000 cholesterol Nutrition 0.000 claims abstract description 48
- 239000003112 inhibitor Substances 0.000 claims abstract description 34
- 150000001875 compounds Chemical class 0.000 claims description 55
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 38
- 210000004027 cell Anatomy 0.000 claims description 36
- 239000012620 biological material Substances 0.000 claims description 27
- 230000001906 cholesterol absorption Effects 0.000 claims description 27
- 210000000110 microvilli Anatomy 0.000 claims description 25
- 229960002685 biotin Drugs 0.000 claims description 22
- 239000011616 biotin Substances 0.000 claims description 22
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 claims description 20
- 235000020958 biotin Nutrition 0.000 claims description 19
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 12
- -1 2-azetidinone compound Chemical class 0.000 claims description 11
- 108010046516 Wheat Germ Agglutinins Proteins 0.000 claims description 11
- 239000006228 supernatant Substances 0.000 claims description 10
- 229920000936 Agarose Polymers 0.000 claims description 7
- 238000002474 experimental method Methods 0.000 claims description 7
- 241000282414 Homo sapiens Species 0.000 claims description 6
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 5
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 5
- 102000035122 glycosylated proteins Human genes 0.000 claims description 4
- 108091005608 glycosylated proteins Proteins 0.000 claims description 4
- 210000000813 small intestine Anatomy 0.000 claims description 4
- 108010051423 streptavidin-agarose Proteins 0.000 claims description 4
- 241000894007 species Species 0.000 claims description 3
- 150000001841 cholesterols Chemical class 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 23
- 239000000047 product Substances 0.000 description 21
- 230000033227 intestinal cholesterol absorption Effects 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 239000007983 Tris buffer Substances 0.000 description 17
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 17
- 210000001519 tissue Anatomy 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000000499 gel Substances 0.000 description 15
- 210000004379 membrane Anatomy 0.000 description 15
- 239000012528 membrane Substances 0.000 description 15
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 14
- 102000023732 binding proteins Human genes 0.000 description 13
- 108091008324 binding proteins Proteins 0.000 description 13
- 239000000872 buffer Substances 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- HEGSGKPQLMEBJL-RKQHYHRCSA-N octyl beta-D-glucopyranoside Chemical compound CCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HEGSGKPQLMEBJL-RKQHYHRCSA-N 0.000 description 11
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 10
- 229930195725 Mannitol Natural products 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- 101710184309 Probable sucrose-6-phosphate hydrolase Proteins 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 102400000472 Sucrase Human genes 0.000 description 10
- 101710112652 Sucrose-6-phosphate hydrolase Proteins 0.000 description 10
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 10
- 235000011073 invertase Nutrition 0.000 description 10
- 239000000594 mannitol Substances 0.000 description 10
- 235000010355 mannitol Nutrition 0.000 description 10
- QZDDFQLIQRYMBV-UHFFFAOYSA-N 2-[3-nitro-2-(2-nitrophenyl)-4-oxochromen-8-yl]acetic acid Chemical compound OC(=O)CC1=CC=CC(C(C=2[N+]([O-])=O)=O)=C1OC=2C1=CC=CC=C1[N+]([O-])=O QZDDFQLIQRYMBV-UHFFFAOYSA-N 0.000 description 9
- 102100022749 Aminopeptidase N Human genes 0.000 description 9
- 108010049990 CD13 Antigens Proteins 0.000 description 9
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 description 9
- 108010052285 Membrane Proteins Proteins 0.000 description 9
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 9
- 239000011324 bead Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 230000002255 enzymatic effect Effects 0.000 description 8
- 210000000936 intestine Anatomy 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 238000005119 centrifugation Methods 0.000 description 7
- 238000005222 photoaffinity labeling Methods 0.000 description 7
- 230000032258 transport Effects 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 210000001367 artery Anatomy 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 108010010234 HDL Lipoproteins Proteins 0.000 description 5
- 102000015779 HDL Lipoproteins Human genes 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 108010090804 Streptavidin Proteins 0.000 description 5
- 238000001042 affinity chromatography Methods 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000003599 detergent Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 238000001962 electrophoresis Methods 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000005855 radiation Effects 0.000 description 5
- 229950005143 sitosterol Drugs 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 241000724266 Broad bean mottle virus Species 0.000 description 4
- 229940113549 Cholesterol inhibitor Drugs 0.000 description 4
- 206010014476 Elevated cholesterol Diseases 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 208000035150 Hypercholesterolemia Diseases 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 102000004895 Lipoproteins Human genes 0.000 description 4
- 108090001030 Lipoproteins Proteins 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 208000011775 arteriosclerosis disease Diseases 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000012872 hydroxylapatite chromatography Methods 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 210000003463 organelle Anatomy 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 4
- YBJHBAHKTGYVGT-UHFFFAOYSA-N 5-(2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl)pentanoic acid Chemical compound N1C(=O)NC2C(CCCCC(=O)O)SCC21 YBJHBAHKTGYVGT-UHFFFAOYSA-N 0.000 description 3
- 206010003210 Arteriosclerosis Diseases 0.000 description 3
- SGNBVLSWZMBQTH-FGAXOLDCSA-N Campesterol Natural products O[C@@H]1CC=2[C@@](C)([C@@H]3[C@H]([C@H]4[C@@](C)([C@H]([C@H](CC[C@H](C(C)C)C)C)CC4)CC3)CC=2)CC1 SGNBVLSWZMBQTH-FGAXOLDCSA-N 0.000 description 3
- BTEISVKTSQLKST-UHFFFAOYSA-N Haliclonasterol Natural products CC(C=CC(C)C(C)(C)C)C1CCC2C3=CC=C4CC(O)CCC4(C)C3CCC12C BTEISVKTSQLKST-UHFFFAOYSA-N 0.000 description 3
- 238000008214 LDL Cholesterol Methods 0.000 description 3
- 108010007622 LDL Lipoproteins Proteins 0.000 description 3
- 102000007330 LDL Lipoproteins Human genes 0.000 description 3
- 102000018697 Membrane Proteins Human genes 0.000 description 3
- 229920004890 Triton X-100 Polymers 0.000 description 3
- 239000013504 Triton X-100 Substances 0.000 description 3
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000003833 bile salt Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- SGNBVLSWZMBQTH-PODYLUTMSA-N campesterol 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)CC[C@@H](C)C(C)C)[C@@]1(C)CC2 SGNBVLSWZMBQTH-PODYLUTMSA-N 0.000 description 3
- 235000000431 campesterol Nutrition 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 238000001085 differential centrifugation Methods 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 210000001198 duodenum Anatomy 0.000 description 3
- 210000001842 enterocyte Anatomy 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 238000013467 fragmentation Methods 0.000 description 3
- 238000006062 fragmentation reaction Methods 0.000 description 3
- 210000003405 ileum Anatomy 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 210000001630 jejunum Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000012064 sodium phosphate buffer Substances 0.000 description 3
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 2
- KKBXLTKVWSOEIJ-UHFFFAOYSA-N 1-(4-aminophenyl)-3-(3-hydroxy-3-phenylpropyl)-4-(3-methoxyphenyl)azetidin-2-one Chemical compound COC1=CC=CC(C2N(C(=O)C2CCC(O)C=2C=CC=CC=2)C=2C=CC(N)=CC=2)=C1 KKBXLTKVWSOEIJ-UHFFFAOYSA-N 0.000 description 2
- AYZCEVRQUAJWBW-UHFFFAOYSA-N 3-[3-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropyl]-4-(3-methoxyphenyl)-1-(4-nitrophenyl)azetidin-2-one Chemical compound COC1=CC=CC(C2N(C(=O)C2CCC(O[Si](C)(C)C(C)(C)C)C=2C=CC=CC=2)C=2C=CC(=CC=2)[N+]([O-])=O)=C1 AYZCEVRQUAJWBW-UHFFFAOYSA-N 0.000 description 2
- LRXBZTWIFDRJSG-UHFFFAOYSA-N 3-[5-[tert-butyl(dimethyl)silyl]oxy-5-phenylpentanoyl]-4-phenyl-1,3-oxazolidin-2-one Chemical compound C=1C=CC=CC=1C(O[Si](C)(C)C(C)(C)C)CCCC(=O)N(C(OC1)=O)C1C1=CC=CC=C1 LRXBZTWIFDRJSG-UHFFFAOYSA-N 0.000 description 2
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108090000317 Chymotrypsin Proteins 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102400000471 Isomaltase Human genes 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 description 2
- 238000011785 NMRI mouse Methods 0.000 description 2
- 108010026867 Oligo-1,6-Glucosidase Proteins 0.000 description 2
- 239000012722 SDS sample buffer Substances 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000009102 absorption Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 210000001789 adipocyte Anatomy 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 210000000941 bile Anatomy 0.000 description 2
- 239000003613 bile acid Substances 0.000 description 2
- 229940093761 bile salts Drugs 0.000 description 2
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 2
- 210000004534 cecum Anatomy 0.000 description 2
- 229960002376 chymotrypsin Drugs 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 229940125797 compound 12 Drugs 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- NLEBIOOXCVAHBD-QKMCSOCLSA-N dodecyl beta-D-maltoside Chemical compound O[C@@H]1[C@@H](O)[C@H](OCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 NLEBIOOXCVAHBD-QKMCSOCLSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 210000003608 fece Anatomy 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000031891 intestinal absorption Effects 0.000 description 2
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 238000005567 liquid scintillation counting Methods 0.000 description 2
- 239000005445 natural material Substances 0.000 description 2
- 230000004903 negative regulation of intestinal cholesterol absorption Effects 0.000 description 2
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
- 235000002378 plant sterols Nutrition 0.000 description 2
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 108020001775 protein parts Proteins 0.000 description 2
- 230000009103 reabsorption Effects 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000003307 slaughter Methods 0.000 description 2
- 238000005063 solubilization Methods 0.000 description 2
- 230000007928 solubilization Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000005556 structure-activity relationship Methods 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 238000010257 thawing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- KZJWDPNRJALLNS-VPUBHVLGSA-N (-)-beta-Sitosterol Natural products O[C@@H]1CC=2[C@@](C)([C@@H]3[C@H]([C@H]4[C@@](C)([C@H]([C@H](CC[C@@H](C(C)C)CC)C)CC4)CC3)CC=2)CC1 KZJWDPNRJALLNS-VPUBHVLGSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- CSVWWLUMXNHWSU-UHFFFAOYSA-N (22E)-(24xi)-24-ethyl-5alpha-cholest-22-en-3beta-ol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(CC)C(C)C)C1(C)CC2 CSVWWLUMXNHWSU-UHFFFAOYSA-N 0.000 description 1
- HQHPJUCPDNPTQJ-JKQORVJESA-N (2S)-2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-(4-azidophenyl)propanoic acid Chemical compound C(CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@H]12)(=O)N[C@@H](CC1=CC=C(C=C1)N=[N+]=[N-])C(=O)O HQHPJUCPDNPTQJ-JKQORVJESA-N 0.000 description 1
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- YZJSVLVRDFIMHX-UHFFFAOYSA-N 1-(4-methoxyphenyl)-n-(4-nitrophenyl)methanimine Chemical compound C1=CC(OC)=CC=C1C=NC1=CC=C([N+]([O-])=O)C=C1 YZJSVLVRDFIMHX-UHFFFAOYSA-N 0.000 description 1
- NDVMCQUOSYOQMZ-UHFFFAOYSA-N 2,2-bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)C(C(N)=O)[Si](C)(C)C NDVMCQUOSYOQMZ-UHFFFAOYSA-N 0.000 description 1
- IDOQDZANRZQBTP-UHFFFAOYSA-N 2-[2-(2,4,4-trimethylpentan-2-yl)phenoxy]ethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=CC=C1OCCO IDOQDZANRZQBTP-UHFFFAOYSA-N 0.000 description 1
- KLEXDBGYSOIREE-UHFFFAOYSA-N 24xi-n-propylcholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CCC)C(C)C)C1(C)CC2 KLEXDBGYSOIREE-UHFFFAOYSA-N 0.000 description 1
- HRGUSFBJBOKSML-UHFFFAOYSA-N 3',5'-di-O-methyltricetin Chemical compound COC1=C(O)C(OC)=CC(C=2OC3=CC(O)=CC(O)=C3C(=O)C=2)=C1 HRGUSFBJBOKSML-UHFFFAOYSA-N 0.000 description 1
- FDDCQWPWXJJNFA-UHFFFAOYSA-N 3-(4-azidophenyl)-2-(9h-fluoren-9-ylmethoxycarbonylamino)propanoic acid Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)NC(C(=O)O)CC1=CC=C(N=[N+]=[N-])C=C1 FDDCQWPWXJJNFA-UHFFFAOYSA-N 0.000 description 1
- LWPWJQSSRSMWGE-UHFFFAOYSA-N 3-(5-hydroxy-5-phenylpentanoyl)-4-phenyl-1,3-oxazolidin-2-one Chemical compound C=1C=CC=CC=1C(O)CCCC(=O)N(C(OC1)=O)C1C1=CC=CC=C1 LWPWJQSSRSMWGE-UHFFFAOYSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- GPUBPSKTFNYPHI-AYGRAXKESA-N 3-[5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoyl]-1-hydroxypyrrolidine-2,5-dione Chemical compound O=C1N(O)C(=O)CC1C(=O)CCCC[C@H]1[C@H]2NC(=O)N[C@H]2CS1 GPUBPSKTFNYPHI-AYGRAXKESA-N 0.000 description 1
- YPRVALBGAROCLB-UHFFFAOYSA-N 3-[5-[tert-butyl(dimethyl)silyl]oxy-2-[(4-methoxyphenyl)-(4-nitroanilino)methyl]-5-phenylpentanoyl]-4-phenyl-1,3-oxazolidin-2-one Chemical compound C1=CC(OC)=CC=C1C(C(CCC(O[Si](C)(C)C(C)(C)C)C=1C=CC=CC=1)C(=O)N1C(OCC1C=1C=CC=CC=1)=O)NC1=CC=C([N+]([O-])=O)C=C1 YPRVALBGAROCLB-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
- ULLSWWGYZWBPHK-UHFFFAOYSA-N 5-(9h-fluoren-9-ylmethoxycarbonylamino)pentanoic acid Chemical compound C1=CC=C2C(COC(=O)NCCCCC(=O)O)C3=CC=CC=C3C2=C1 ULLSWWGYZWBPHK-UHFFFAOYSA-N 0.000 description 1
- QRIONSRADSROOL-UHFFFAOYSA-N 5-amino-n-[4-[3-(3-hydroxy-3-phenylpropyl)-2-(4-methoxyphenyl)-4-oxoazetidin-1-yl]phenyl]pentanamide Chemical compound C1=CC(OC)=CC=C1C1N(C=2C=CC(NC(=O)CCCCN)=CC=2)C(=O)C1CCC(O)C1=CC=CC=C1 QRIONSRADSROOL-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108010004103 Chylomicrons Proteins 0.000 description 1
- LPZCCMIISIBREI-MTFRKTCUSA-N Citrostadienol Natural products CC=C(CC[C@@H](C)[C@H]1CC[C@H]2C3=CC[C@H]4[C@H](C)[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)C(C)C LPZCCMIISIBREI-MTFRKTCUSA-N 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- ARVGMISWLZPBCH-UHFFFAOYSA-N Dehydro-beta-sitosterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)CCC(CC)C(C)C)CCC33)C)C3=CC=C21 ARVGMISWLZPBCH-UHFFFAOYSA-N 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 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 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 239000011837 N,N-methylenebisacrylamide Substances 0.000 description 1
- LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
- BNSTVBLCTRZUDD-KEWYIRBNSA-N N-[(3R,4S,5S,6R)-2,3,4,5-tetrahydroxy-6-(hydroxymethyl)oxan-2-yl]acetamide Chemical compound CC(=O)NC1(O)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O BNSTVBLCTRZUDD-KEWYIRBNSA-N 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- BNSTVBLCTRZUDD-CBQIKETKSA-N N-acetyl-D-glucoseamine Chemical compound CC(=O)N[C@@]1(O)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O BNSTVBLCTRZUDD-CBQIKETKSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000000447 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Human genes 0.000 description 1
- 108010055817 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Proteins 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- IDDMFNIRSJVBHE-UHFFFAOYSA-N Piscigenin Natural products COC1=C(O)C(OC)=CC(C=2C(C3=C(O)C=C(O)C=C3OC=2)=O)=C1 IDDMFNIRSJVBHE-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- UZMAPBJVXOGOFT-UHFFFAOYSA-N Syringetin Natural products COC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UZMAPBJVXOGOFT-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 239000007997 Tricine buffer Substances 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 229920004929 Triton X-114 Polymers 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 239000001166 ammonium sulphate Substances 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003529 anticholesteremic agent Substances 0.000 description 1
- 229940127226 anticholesterol agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- MJVXAPPOFPTTCA-UHFFFAOYSA-N beta-Sistosterol Natural products CCC(CCC(C)C1CCC2C3CC=C4C(C)C(O)CCC4(C)C3CCC12C)C(C)C MJVXAPPOFPTTCA-UHFFFAOYSA-N 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000012832 cell culture technique Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 210000002711 centrocyte Anatomy 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 230000031154 cholesterol homeostasis Effects 0.000 description 1
- 238000009838 combustion analysis Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 208000028831 congenital heart disease Diseases 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- LBJNMUFDOHXDFG-UHFFFAOYSA-N copper;hydrate Chemical compound O.[Cu].[Cu] LBJNMUFDOHXDFG-UHFFFAOYSA-N 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- WOQQAWHSKSSAGF-WXFJLFHKSA-N decyl beta-D-maltopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](OCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 WOQQAWHSKSSAGF-WXFJLFHKSA-N 0.000 description 1
- 230000022811 deglycosylation Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- LCFXLZAXGXOXAP-UHFFFAOYSA-N ethyl 2-cyano-2-hydroxyiminoacetate Chemical compound CCOC(=O)C(=NO)C#N LCFXLZAXGXOXAP-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 1
- 229960000815 ezetimibe Drugs 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 229940028435 intralipid Drugs 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- IZWSFJTYBVKZNK-UHFFFAOYSA-N lauryl sulfobetaine Chemical compound CCCCCCCCCCCC[N+](C)(C)CCCS([O-])(=O)=O IZWSFJTYBVKZNK-UHFFFAOYSA-N 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 210000001853 liver microsome Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- VWMZIGBYZQUQOA-QEEMJVPDSA-N pamaqueside Chemical compound O([C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4C[C@H]5[C@@H]([C@]4(CC(=O)[C@@H]3[C@@]2(C)CC1)C)[C@@H]([C@]1(OC[C@H](C)CC1)O5)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VWMZIGBYZQUQOA-QEEMJVPDSA-N 0.000 description 1
- 229950005482 pamaqueside Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000007856 photoaffinity label Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 235000015277 pork Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 210000004777 protein coat Anatomy 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000000163 radioactive labelling Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol 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)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 235000015500 sitosterol Nutrition 0.000 description 1
- NLQLSVXGSXCXFE-UHFFFAOYSA-N sitosterol Natural products CC=C(/CCC(C)C1CC2C3=CCC4C(C)C(O)CCC4(C)C3CCC2(C)C1)C(C)C NLQLSVXGSXCXFE-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 235000000891 standard diet Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- BMCJATLPEJCACU-UHFFFAOYSA-N tricin Natural products COc1cc(OC)c(O)c(c1)C2=CC(=O)c3c(O)cc(O)cc3O2 BMCJATLPEJCACU-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 239000002691 unilamellar liposome Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
-
- 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)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Analytical Chemistry (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP02017504 | 2002-08-06 | ||
PCT/EP2003/008290 WO2004014947A1 (en) | 2002-08-06 | 2003-07-28 | Method for isolating an intestinal cholesterol binding protein |
Publications (2)
Publication Number | Publication Date |
---|---|
NO20051169L NO20051169L (no) | 2005-05-02 |
NO333437B1 true NO333437B1 (no) | 2013-06-03 |
Family
ID=31502689
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20051169A NO333437B1 (no) | 2002-08-06 | 2005-03-04 | Fremgangsmate for a isolere et intestinalt kolesterolbindende protein, sammensetning samt anvendelse av sammensetningen |
NO20130115A NO20130115L (no) | 2002-08-06 | 2013-01-18 | Farmasøytisk sammensetning omfattende et intestinalt kolesterolbindende protein. |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20130115A NO20130115L (no) | 2002-08-06 | 2013-01-18 | Farmasøytisk sammensetning omfattende et intestinalt kolesterolbindende protein. |
Country Status (17)
Country | Link |
---|---|
US (2) | US7435727B2 (zh) |
EP (1) | EP1529061B1 (zh) |
JP (1) | JP4575772B2 (zh) |
KR (1) | KR101095288B1 (zh) |
CN (1) | CN1330667C (zh) |
AT (1) | ATE386053T1 (zh) |
AU (1) | AU2003253341C1 (zh) |
BR (1) | BR0313217A (zh) |
CA (1) | CA2493487C (zh) |
DE (1) | DE60319093T2 (zh) |
HK (1) | HK1082509A1 (zh) |
IL (2) | IL166492A (zh) |
MX (1) | MXPA05001264A (zh) |
NO (2) | NO333437B1 (zh) |
RU (1) | RU2345089C2 (zh) |
WO (1) | WO2004014947A1 (zh) |
ZA (1) | ZA200500053B (zh) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0215579D0 (en) | 2002-07-05 | 2002-08-14 | Astrazeneca Ab | Chemical compounds |
US7135556B2 (en) | 2002-07-19 | 2006-11-14 | Schering Corporation | NPC1L1 (NPC3) and methods of use thereof |
AU2004303742B2 (en) | 2003-12-23 | 2008-06-19 | Astrazeneca Ab | Diphenylazetidinone derivatives possessing cholesterol absorption inhibitory activity |
EP1723414A4 (en) | 2004-01-16 | 2008-03-26 | Merck & Co Inc | NPC1L1 (NPC3) AND METHOD FOR IDENTIFYING ITS LIGANDS |
CN101243072A (zh) | 2005-06-20 | 2008-08-13 | 先灵公司 | 用作组胺h3拮抗剂的哌啶衍生物 |
SA06270191B1 (ar) | 2005-06-22 | 2010-03-29 | استرازينيكا ايه بي | مشتقات من 2- أزيتيدينون جديدة باعتبارها مثبطات لامتصاص الكوليسترول لعلاج حالات فرط نسبة الدهون في الدم |
WO2007100807A2 (en) | 2006-02-24 | 2007-09-07 | Schering Corporation | Npc1l1 orthologues |
AR060623A1 (es) | 2006-04-27 | 2008-07-02 | Astrazeneca Ab | Compuestos derivados de 2-azetidinona y un metodo de preparacion |
CN1869704B (zh) * | 2006-06-14 | 2010-06-30 | 厦门大学 | 快速鉴定与病原菌互作的宿主蛋白的方法 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4710469A (en) * | 1986-05-02 | 1987-12-01 | Merck & Co., Inc. | Novel phosphotyrosyl protein phosphatase |
CA2002607C (en) | 1988-11-10 | 2004-01-27 | Gordon G. Wong | Natural killer stimulatory factor |
ES2168091T3 (es) * | 1990-05-16 | 2002-06-01 | Genetics Inst | Proteinas de induccion osea y cartilaginosa. |
US5264372A (en) | 1991-03-15 | 1993-11-23 | Amylin Pharmaceuticals, Inc. | Receptor-based screening methods for amylin agonists and antagonists |
US5518911A (en) | 1995-01-06 | 1996-05-21 | Onyx Pharmaceuticals, Inc. | Human PAK65 |
JP3088681B2 (ja) | 1997-05-22 | 2000-09-18 | 宮城県 | 形質膜局在シアリダーゼ及びそれをコードするdna |
US6383734B1 (en) | 1998-09-30 | 2002-05-07 | Advanced Research And Technology Institute, Inc. | Method to determine inhibition of PAK3 activation of Raf-1 |
JP2000166545A (ja) * | 1998-12-07 | 2000-06-20 | Snow Brand Milk Prod Co Ltd | 胆汁酸活性化リパーゼ |
AU3566200A (en) | 1999-04-01 | 2000-10-23 | Astrazeneca Uk Limited | Human signal transduction serine/threonine protein kinase |
AU4343500A (en) * | 1999-04-16 | 2000-11-02 | Schering Corporation | Use of azetidinone compounds |
DE10042447A1 (de) * | 2000-08-29 | 2002-03-28 | Aventis Pharma Gmbh | Protein aus dem Darm von Wirbeltieren, welches Cholesterin absorbiert, sowie Verwendung dieses Proteins zur Identifizierung von Inhibitoren des intestinalen Cholesterintransports |
-
2003
- 2003-07-28 KR KR1020057002084A patent/KR101095288B1/ko not_active IP Right Cessation
- 2003-07-28 BR BR0313217-0A patent/BR0313217A/pt not_active IP Right Cessation
- 2003-07-28 CA CA2493487A patent/CA2493487C/en not_active Expired - Fee Related
- 2003-07-28 CN CNB038173328A patent/CN1330667C/zh not_active Expired - Fee Related
- 2003-07-28 DE DE60319093T patent/DE60319093T2/de not_active Expired - Lifetime
- 2003-07-28 WO PCT/EP2003/008290 patent/WO2004014947A1/en active IP Right Grant
- 2003-07-28 JP JP2004526798A patent/JP4575772B2/ja not_active Expired - Fee Related
- 2003-07-28 AT AT03784089T patent/ATE386053T1/de not_active IP Right Cessation
- 2003-07-28 AU AU2003253341A patent/AU2003253341C1/en not_active Ceased
- 2003-07-28 RU RU2005106238/13A patent/RU2345089C2/ru not_active IP Right Cessation
- 2003-07-28 EP EP03784089A patent/EP1529061B1/en not_active Expired - Lifetime
- 2003-07-28 MX MXPA05001264A patent/MXPA05001264A/es active IP Right Grant
- 2003-08-06 US US10/635,008 patent/US7435727B2/en not_active Expired - Fee Related
-
2005
- 2005-01-04 ZA ZA200500053A patent/ZA200500053B/en unknown
- 2005-01-25 IL IL166492A patent/IL166492A/en not_active IP Right Cessation
- 2005-03-04 NO NO20051169A patent/NO333437B1/no not_active IP Right Cessation
-
2006
- 2006-03-13 HK HK06103145A patent/HK1082509A1/xx unknown
-
2007
- 2007-10-16 US US11/872,855 patent/US7786103B2/en not_active Expired - Fee Related
-
2009
- 2009-06-17 IL IL199409A patent/IL199409A/en not_active IP Right Cessation
-
2013
- 2013-01-18 NO NO20130115A patent/NO20130115L/no not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
CN1330667C (zh) | 2007-08-08 |
DE60319093T2 (de) | 2009-02-05 |
BR0313217A (pt) | 2005-06-14 |
US7435727B2 (en) | 2008-10-14 |
AU2003253341C1 (en) | 2009-09-24 |
US20080167451A1 (en) | 2008-07-10 |
ZA200500053B (en) | 2006-07-26 |
JP4575772B2 (ja) | 2010-11-04 |
IL166492A0 (en) | 2006-01-15 |
CA2493487C (en) | 2013-01-22 |
JP2006512054A (ja) | 2006-04-13 |
US20040126812A1 (en) | 2004-07-01 |
RU2345089C2 (ru) | 2009-01-27 |
US7786103B2 (en) | 2010-08-31 |
AU2003253341A1 (en) | 2004-02-25 |
ATE386053T1 (de) | 2008-03-15 |
RU2005106238A (ru) | 2005-08-27 |
WO2004014947A1 (en) | 2004-02-19 |
DE60319093D1 (de) | 2008-03-27 |
CA2493487A1 (en) | 2004-02-19 |
KR101095288B1 (ko) | 2011-12-16 |
KR20060015443A (ko) | 2006-02-17 |
IL199409A (en) | 2010-12-30 |
EP1529061B1 (en) | 2008-02-13 |
CN1668642A (zh) | 2005-09-14 |
EP1529061A1 (en) | 2005-05-11 |
AU2003253341B2 (en) | 2009-04-23 |
HK1082509A1 (en) | 2006-06-09 |
IL166492A (en) | 2010-12-30 |
MXPA05001264A (es) | 2005-04-28 |
NO20051169L (no) | 2005-05-02 |
NO20130115L (no) | 2005-05-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO20130115L (no) | Farmasøytisk sammensetning omfattende et intestinalt kolesterolbindende protein. | |
US6794359B2 (en) | Vertebrate intestinal protein which absorbs cholesterol, its inhibitors and mehtod of identifying the same | |
DE69837678T2 (de) | Compositions zur inhibierung der proliferation glatter muskulatur und verfahren zur diagnose von arteriosklerose | |
Hoogenboom et al. | Absorption of a mutagenic metabolite released from protein-bound residues of furazolidone | |
DE102005029845B4 (de) | Verfahren zur Diagnose von rheumatischen Erkrankungen | |
DE69736351T4 (de) | Methoden und mittel zur hemmung der cdk4-aktivität | |
US6743769B1 (en) | Antimicrobial peptides and derived metapeptides | |
Váradi et al. | Synthesis of PAF, an antifungal protein from P. chrysogenum, by native chemical ligation: native disulfide pattern and fold obtained upon oxidative refolding | |
Monti et al. | N-acetylcysteine treatment ameliorates the skeletal phenotype of a mouse model of diastrophic dysplasia | |
Kisilevsky et al. | Pathogenesis of amyloidosis | |
EP0854722A1 (en) | Proteins involved in targeting of peptidyl transfer center, and corresponding therapeutic agents and methods | |
Murariu et al. | Synthesis and mass spectrometric characterization of a metal-affinity decapeptide: Copper-induced conformational changes | |
JP2004510967A (ja) | イソプレノイド依存rasアンカー(idra)タンパク質 | |
JP2007205777A (ja) | 変形性関節症の診断支援方法 | |
DE19845434C1 (de) | Gewebebindende Peptide, ihre Identifizierung, Herstellung und Verwendung | |
Al Omireeni et al. | EFFECT OF MAGNESIUM CHLORIDE AND SODIUM FLUORIDE ON VARIOUS HYDROXYPROLINE FRACTIONS IN RAT KIDNEYS | |
KR20000037812A (ko) | 엔지오제닌 및 플라즈민의 저해제 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |