ES2294802T3 - Hidrolasa de amidas de acidos grasos. - Google Patents
Hidrolasa de amidas de acidos grasos. Download PDFInfo
- Publication number
- ES2294802T3 ES2294802T3 ES97948210T ES97948210T ES2294802T3 ES 2294802 T3 ES2294802 T3 ES 2294802T3 ES 97948210 T ES97948210 T ES 97948210T ES 97948210 T ES97948210 T ES 97948210T ES 2294802 T3 ES2294802 T3 ES 2294802T3
- Authority
- ES
- Spain
- Prior art keywords
- baselineskip
- faah
- seq
- cis
- amide
- 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.)
- Expired - Lifetime
Links
- 235000014113 dietary fatty acids Nutrition 0.000 title claims abstract description 55
- 239000000194 fatty acid Substances 0.000 title claims abstract description 55
- 229930195729 fatty acid Natural products 0.000 title claims abstract description 55
- 150000004665 fatty acids Chemical class 0.000 title claims description 53
- 108010046094 fatty-acid amide hydrolase Proteins 0.000 claims abstract description 138
- 102100029111 Fatty-acid amide hydrolase 1 Human genes 0.000 claims abstract description 116
- FATBGEAMYMYZAF-KTKRTIGZSA-N oleamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(N)=O FATBGEAMYMYZAF-KTKRTIGZSA-N 0.000 claims abstract description 84
- 230000007062 hydrolysis Effects 0.000 claims abstract description 31
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 31
- 239000003112 inhibitor Substances 0.000 claims abstract description 27
- 102000004157 Hydrolases Human genes 0.000 claims abstract description 16
- 108090000604 Hydrolases Proteins 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims description 42
- 238000006243 chemical reaction Methods 0.000 claims description 37
- 238000004587 chromatography analysis Methods 0.000 claims description 37
- LGEQQWMQCRIYKG-UHFFFAOYSA-N arachidonic acid ethanolamide Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)NCCO LGEQQWMQCRIYKG-UHFFFAOYSA-N 0.000 claims description 34
- LGEQQWMQCRIYKG-DOFZRALJSA-N anandamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCO LGEQQWMQCRIYKG-DOFZRALJSA-N 0.000 claims description 31
- 238000010828 elution Methods 0.000 claims description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 29
- 239000002773 nucleotide Substances 0.000 claims description 26
- 125000003729 nucleotide group Chemical group 0.000 claims description 26
- LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 claims description 17
- 239000000758 substrate Substances 0.000 claims description 17
- 125000000539 amino acid group Chemical group 0.000 claims description 16
- 108020004707 nucleic acids Proteins 0.000 claims description 15
- 102000039446 nucleic acids Human genes 0.000 claims description 15
- 150000007523 nucleic acids Chemical class 0.000 claims description 15
- 150000001408 amides Chemical class 0.000 claims description 12
- 238000001042 affinity chromatography Methods 0.000 claims description 10
- HSEMFIZWXHQJAE-UHFFFAOYSA-N hexadecanamide Chemical compound CCCCCCCCCCCCCCCC(N)=O HSEMFIZWXHQJAE-UHFFFAOYSA-N 0.000 claims description 10
- FHUDAMLDXFJHJE-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-one Chemical compound CC(=O)C(F)(F)F FHUDAMLDXFJHJE-UHFFFAOYSA-N 0.000 claims description 9
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 claims description 8
- 239000003940 fatty acid amidase inhibitor Substances 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 6
- 229960002897 heparin Drugs 0.000 claims description 6
- 229920000669 heparin Polymers 0.000 claims description 6
- 238000000338 in vitro Methods 0.000 claims description 6
- LYRFLYHAGKPMFH-UHFFFAOYSA-N octadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(N)=O LYRFLYHAGKPMFH-UHFFFAOYSA-N 0.000 claims description 6
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 6
- QEALYLRSRQDCRA-UHFFFAOYSA-N myristamide Chemical compound CCCCCCCCCCCCCC(N)=O QEALYLRSRQDCRA-UHFFFAOYSA-N 0.000 claims description 5
- 150000003140 primary amides Chemical class 0.000 claims description 5
- 239000007790 solid phase Substances 0.000 claims description 5
- 239000003463 adsorbent Substances 0.000 claims description 3
- 239000013604 expression vector Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000011002 quantification Methods 0.000 claims description 2
- 101000937693 Homo sapiens Fatty acid 2-hydroxylase Proteins 0.000 claims 21
- 101000918494 Homo sapiens Fatty-acid amide hydrolase 1 Proteins 0.000 claims 21
- 229940124036 Hydrolase inhibitor Drugs 0.000 claims 1
- 108020004511 Recombinant DNA Proteins 0.000 claims 1
- 235000021355 Stearic acid Nutrition 0.000 claims 1
- 239000004093 hydrolase inhibitor Substances 0.000 claims 1
- 238000004255 ion exchange chromatography Methods 0.000 claims 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims 1
- 239000008117 stearic acid Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 55
- 108090000623 proteins and genes Proteins 0.000 abstract description 44
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 abstract description 28
- 150000001875 compounds Chemical class 0.000 abstract description 26
- 239000005642 Oleic acid Substances 0.000 abstract description 22
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 abstract description 21
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 abstract description 21
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 abstract description 21
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 abstract description 21
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 abstract description 21
- 230000015572 biosynthetic process Effects 0.000 abstract description 10
- -1 fatty acid primary amides Chemical class 0.000 abstract description 9
- 230000002557 soporific effect Effects 0.000 abstract description 7
- 150000001413 amino acids Chemical class 0.000 description 98
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 97
- 241000700159 Rattus Species 0.000 description 91
- 239000002299 complementary DNA Substances 0.000 description 69
- 108090000765 processed proteins & peptides Proteins 0.000 description 59
- 239000012634 fragment Substances 0.000 description 56
- 239000000243 solution Substances 0.000 description 54
- 210000004027 cell Anatomy 0.000 description 49
- 239000011541 reaction mixture Substances 0.000 description 45
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 44
- 230000002829 reductive effect Effects 0.000 description 44
- 235000019439 ethyl acetate Nutrition 0.000 description 43
- 102000004169 proteins and genes Human genes 0.000 description 40
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 34
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 30
- 210000004556 brain Anatomy 0.000 description 30
- 108700023418 Amidases Proteins 0.000 description 29
- 102000005922 amidase Human genes 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 210000004185 liver Anatomy 0.000 description 24
- 239000012528 membrane Substances 0.000 description 24
- 230000007958 sleep Effects 0.000 description 23
- 229910052681 coesite Inorganic materials 0.000 description 22
- 229910052906 cristobalite Inorganic materials 0.000 description 22
- 239000000377 silicon dioxide Substances 0.000 description 22
- 235000012239 silicon dioxide Nutrition 0.000 description 22
- 229910052682 stishovite Inorganic materials 0.000 description 22
- 229910052905 tridymite Inorganic materials 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 102000004190 Enzymes Human genes 0.000 description 20
- 108090000790 Enzymes Proteins 0.000 description 20
- FATBGEAMYMYZAF-UHFFFAOYSA-N oleicacidamide-heptaglycolether Natural products CCCCCCCCC=CCCCCCCCC(N)=O FATBGEAMYMYZAF-UHFFFAOYSA-N 0.000 description 20
- 239000012071 phase Substances 0.000 description 20
- 229920006395 saturated elastomer Chemical class 0.000 description 20
- 239000000047 product Substances 0.000 description 18
- 125000003275 alpha amino acid group Chemical group 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- 239000000284 extract Substances 0.000 description 16
- 239000012074 organic phase Substances 0.000 description 16
- 238000012546 transfer Methods 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000007832 Na2SO4 Substances 0.000 description 15
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
- 229910052938 sodium sulfate Inorganic materials 0.000 description 15
- 235000011152 sodium sulphate Nutrition 0.000 description 15
- 108020004999 messenger RNA Proteins 0.000 description 14
- 239000011780 sodium chloride Substances 0.000 description 14
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 14
- 239000002253 acid Substances 0.000 description 13
- 102000004196 processed proteins & peptides Human genes 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 12
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
- 239000013615 primer Substances 0.000 description 12
- 239000000523 sample Substances 0.000 description 12
- 239000006228 supernatant Substances 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 10
- 239000012230 colorless oil Substances 0.000 description 10
- 230000002255 enzymatic effect Effects 0.000 description 10
- 238000004809 thin layer chromatography Methods 0.000 description 10
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 9
- 101150065749 Churc1 gene Proteins 0.000 description 9
- 102100038239 Protein Churchill Human genes 0.000 description 9
- VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical class FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 description 9
- 238000009396 hybridization Methods 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 108091026890 Coding region Proteins 0.000 description 8
- 108020004705 Codon Proteins 0.000 description 8
- 230000006399 behavior Effects 0.000 description 8
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 210000000170 cell membrane Anatomy 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 239000013067 intermediate product Substances 0.000 description 7
- 150000002632 lipids Chemical class 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- 239000011324 bead Substances 0.000 description 6
- 230000000977 initiatory effect Effects 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 229930182817 methionine Natural products 0.000 description 6
- RIZOOQYPYGPBOC-UHFFFAOYSA-N methyl 9-hydroxynonanoate Chemical compound COC(=O)CCCCCCCCO RIZOOQYPYGPBOC-UHFFFAOYSA-N 0.000 description 6
- 230000011664 signaling Effects 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 102000004092 Amidohydrolases Human genes 0.000 description 5
- 108090000531 Amidohydrolases Proteins 0.000 description 5
- 108010052285 Membrane Proteins Proteins 0.000 description 5
- 102000018697 Membrane Proteins Human genes 0.000 description 5
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
- 108020005038 Terminator Codon Proteins 0.000 description 5
- HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 5
- 229940114079 arachidonic acid Drugs 0.000 description 5
- 235000021342 arachidonic acid Nutrition 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 238000000265 homogenisation Methods 0.000 description 5
- ADTIBIOIERBRIB-UHFFFAOYSA-N methyl 8-hydroxyoctanoate Chemical compound COC(=O)CCCCCCCO ADTIBIOIERBRIB-UHFFFAOYSA-N 0.000 description 5
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 5
- 230000036961 partial effect Effects 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 239000013049 sediment Substances 0.000 description 5
- 238000012163 sequencing technique Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 108010067770 Endopeptidase K Proteins 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- 102000004142 Trypsin Human genes 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 230000003301 hydrolyzing effect Effects 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 238000005342 ion exchange Methods 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 229920000136 polysorbate Polymers 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- 239000003155 DNA primer Substances 0.000 description 3
- 108700026244 Open Reading Frames Proteins 0.000 description 3
- 208000010340 Sleep Deprivation Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 229920004890 Triton X-100 Polymers 0.000 description 3
- 239000013504 Triton X-100 Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 238000000211 autoradiogram Methods 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- RCTYPNKXASFOBE-UHFFFAOYSA-M chloromercury Chemical compound [Hg]Cl RCTYPNKXASFOBE-UHFFFAOYSA-M 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 210000001320 hippocampus Anatomy 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- SPAKMVQVTSVXES-UHFFFAOYSA-N methanol;oxolane;hydrate Chemical compound O.OC.C1CCOC1 SPAKMVQVTSVXES-UHFFFAOYSA-N 0.000 description 3
- 210000001589 microsome Anatomy 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000012679 serum free medium Substances 0.000 description 3
- 230000037322 slow-wave sleep Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 230000001360 synchronised effect Effects 0.000 description 3
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 239000012588 trypsin Substances 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 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 2
- WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- QEFCUDIECDGSLC-UHFFFAOYSA-N 9-[tert-butyl(diphenyl)silyl]oxynonanal Chemical compound C=1C=CC=CC=1[Si](OCCCCCCCCC=O)(C(C)(C)C)C1=CC=CC=C1 QEFCUDIECDGSLC-UHFFFAOYSA-N 0.000 description 2
- XEGRKZRPTBNSMN-UHFFFAOYSA-N 9-bromononanoic acid Chemical compound OC(=O)CCCCCCCCBr XEGRKZRPTBNSMN-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 102100038385 Coiled-coil domain-containing protein R3HCC1L Human genes 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 235000019750 Crude protein Nutrition 0.000 description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 230000005526 G1 to G0 transition Effects 0.000 description 2
- 101000743767 Homo sapiens Coiled-coil domain-containing protein R3HCC1L Proteins 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 206010029260 Neuroblastoma Diseases 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 108090000244 Rat Proteins Proteins 0.000 description 2
- 102000000395 SH3 domains Human genes 0.000 description 2
- 108050008861 SH3 domains Proteins 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 150000003857 carboxamides Chemical class 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000037029 cross reaction Effects 0.000 description 2
- KSMVZQYAVGTKIV-UHFFFAOYSA-N decanal Chemical compound CCCCCCCCCC=O KSMVZQYAVGTKIV-UHFFFAOYSA-N 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000001641 gel filtration chromatography Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 239000011049 pearl Substances 0.000 description 2
- 238000011533 pre-incubation Methods 0.000 description 2
- 230000036385 rapid eye movement (rem) sleep Effects 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 210000002330 subarachnoid space Anatomy 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 230000002618 waking effect Effects 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- MRXDGVXSWIXTQL-HYHFHBMOSA-N (2s)-2-[[(1s)-1-(2-amino-1,4,5,6-tetrahydropyrimidin-6-yl)-2-[[(2s)-4-methyl-1-oxo-1-[[(2s)-1-oxo-3-phenylpropan-2-yl]amino]pentan-2-yl]amino]-2-oxoethyl]carbamoylamino]-3-phenylpropanoic acid Chemical compound C([C@H](NC(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C=O)C1NC(N)=NCC1)C(O)=O)C1=CC=CC=C1 MRXDGVXSWIXTQL-HYHFHBMOSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
- 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 1
- AXAVXPMQTGXXJZ-UHFFFAOYSA-N 2-aminoacetic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol Chemical compound NCC(O)=O.OCC(N)(CO)CO AXAVXPMQTGXXJZ-UHFFFAOYSA-N 0.000 description 1
- KIBVFIDMXQZCBS-UHFFFAOYSA-N 2-methyloctanedioic acid Chemical compound OC(=O)C(C)CCCCCC(O)=O KIBVFIDMXQZCBS-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- PLWROONZUDKYKG-DOFZRALJSA-N AACOCF3 Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)C(F)(F)F PLWROONZUDKYKG-DOFZRALJSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000589155 Agrobacterium tumefaciens Species 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- YZXBAPSDXZZRGB-DOFZRALJSA-M Arachidonate Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC([O-])=O YZXBAPSDXZZRGB-DOFZRALJSA-M 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000351920 Aspergillus nidulans Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- OBMZMSLWNNWEJA-XNCRXQDQSA-N C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 Chemical compound C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 OBMZMSLWNNWEJA-XNCRXQDQSA-N 0.000 description 1
- 241000244203 Caenorhabditis elegans Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- OLVPQBGMUGIKIW-UHFFFAOYSA-N Chymostatin Natural products C=1C=CC=CC=1CC(C=O)NC(=O)C(C(C)CC)NC(=O)C(C1NC(N)=NCC1)NC(=O)NC(C(O)=O)CC1=CC=CC=C1 OLVPQBGMUGIKIW-UHFFFAOYSA-N 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 206010052804 Drug tolerance Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- UAUDZVJPLUQNMU-UHFFFAOYSA-N Erucasaeureamid Natural products CCCCCCCCC=CCCCCCCCCCCCC(N)=O UAUDZVJPLUQNMU-UHFFFAOYSA-N 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000010909 Monoamine Oxidase Human genes 0.000 description 1
- 108010062431 Monoamine oxidase Proteins 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 101710176384 Peptide 1 Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 108091036407 Polyadenylation Proteins 0.000 description 1
- 206010062519 Poor quality sleep Diseases 0.000 description 1
- 241001148183 Pseudomonas savastanoi Species 0.000 description 1
- 244000088415 Raphanus sativus Species 0.000 description 1
- 235000006140 Raphanus sativus var sativus Nutrition 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 229940122055 Serine protease inhibitor Drugs 0.000 description 1
- 101710102218 Serine protease inhibitor Proteins 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical compound [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000036626 alertness Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229940114078 arachidonate Drugs 0.000 description 1
- 210000000576 arachnoid Anatomy 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- SISAYUDTHCIGLM-UHFFFAOYSA-N bromine dioxide Inorganic materials O=Br=O SISAYUDTHCIGLM-UHFFFAOYSA-N 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 210000002987 choroid plexus Anatomy 0.000 description 1
- 108010086192 chymostatin Proteins 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- CEJLBZWIKQJOAT-UHFFFAOYSA-N dichloroisocyanuric acid Chemical compound ClN1C(=O)NC(=O)N(Cl)C1=O CEJLBZWIKQJOAT-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- UAUDZVJPLUQNMU-KTKRTIGZSA-N erucamide Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(N)=O UAUDZVJPLUQNMU-KTKRTIGZSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004424 eye movement Effects 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000007863 gel particle Substances 0.000 description 1
- 230000026781 habituation Effects 0.000 description 1
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
- 229960003132 halothane Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 210000003140 lateral ventricle Anatomy 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 201000003631 narcolepsy Diseases 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000000956 olfactory bulb Anatomy 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 210000003455 parietal bone Anatomy 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 108091005706 peripheral membrane proteins Proteins 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 230000001144 postural effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000004461 rapid eye movement Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000009154 spontaneous behavior Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000001768 subcellular fraction Anatomy 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 150000004799 α-ketoamides Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C233/09—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an acyclic unsaturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
- C07C327/20—Esters of monothiocarboxylic acids
- C07C327/22—Esters of monothiocarboxylic acids having carbon atoms of esterified thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
- C07C49/227—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
- C07C57/03—Monocarboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/54—Quaternary phosphonium compounds
- C07F9/5407—Acyclic saturated phosphonium compounds
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
- C12N9/80—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in linear amides (3.5.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/99—Enzyme inactivation by chemical treatment
-
- 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
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/64—Fats; Fatty oils; Ester-type waxes; Higher fatty acids, i.e. having at least seven carbon atoms in an unbroken chain bound to a carboxyl group; Oxidised oils or fats
- C12P7/6409—Fatty acids
- C12P7/6418—Fatty acids by hydrolysis of fatty acid esters
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Anesthesiology (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Fats And Perfumes (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US743168 | 1996-11-04 | ||
| US08/743,168 US6271015B1 (en) | 1995-06-12 | 1996-11-04 | Fatty-acid amide hydrolase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2294802T3 true ES2294802T3 (es) | 2008-04-01 |
Family
ID=24987760
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES97948210T Expired - Lifetime ES2294802T3 (es) | 1996-11-04 | 1997-11-04 | Hidrolasa de amidas de acidos grasos. |
Country Status (10)
| Country | Link |
|---|---|
| US (3) | US6271015B1 (https=) |
| EP (1) | EP0970195B1 (https=) |
| JP (1) | JP4102445B2 (https=) |
| AT (1) | ATE376055T1 (https=) |
| AU (1) | AU739962B2 (https=) |
| CA (1) | CA2270293A1 (https=) |
| DE (1) | DE69738221T2 (https=) |
| DK (1) | DK0970195T3 (https=) |
| ES (1) | ES2294802T3 (https=) |
| WO (1) | WO1998020119A1 (https=) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE443526T1 (de) * | 1999-08-20 | 2009-10-15 | Takeda Pharmaceutical | Zusammensetzung für perkutane absorption mit einem melantoninrezeptor-agonistisch wirkendem wirkstoff |
| AU2002338329B2 (en) | 2001-03-27 | 2006-09-07 | The Regents Of The University Of California | Methods, compounds, and compositions for reducing body fat and modulating fatty acid metabolism |
| US20050054730A1 (en) * | 2001-03-27 | 2005-03-10 | The Regents Of The University Of California | Compounds, compositions and treatment of oleoylethanolamide-like modulators of PPARalpha |
| AU2002311784B2 (en) * | 2001-03-29 | 2007-11-22 | Michael Davis | Acute pharmacologic augmentation of psychotherapy with enhancers of learning or conditioning |
| US9493806B2 (en) | 2001-06-01 | 2016-11-15 | Colorado State University Research Foundation | Enzymatic biosensing systems |
| US8323956B2 (en) * | 2001-06-01 | 2012-12-04 | Colorado State University Research Foundation | Distal tip of biosensor transducer comprising enzyme for deamination |
| US9493805B2 (en) * | 2001-06-01 | 2016-11-15 | Colorado State University Research Foundation | Enzymatic biosensors with enhanced activity retention for detection of organic compounds |
| EP1558591B1 (en) * | 2002-10-07 | 2014-05-07 | The Regents of The University of California | Modulation of anxiety through blockade of anandamide hydrolysis |
| US7765162B2 (en) * | 2002-10-07 | 2010-07-27 | Mastercard International Incorporated | Method and system for conducting off-line and on-line pre-authorized payment transactions |
| US20080124275A1 (en) * | 2002-11-14 | 2008-05-29 | The Scripps Research Institute | Crystalline Form of Fatty Acid Amide Hydrolase (Faah) |
| JP2007509066A (ja) * | 2003-10-16 | 2007-04-12 | ザ・レジェンツ・オブ・ザ・ユニバーシティ・オブ・カリフォルニア | 体脂肪を減らし、食欲を抑制し、脂肪酸代謝を調節するための食物および他の組成物、化合物ならびに方法 |
| US8086315B2 (en) | 2004-02-12 | 2011-12-27 | Asap Medical, Inc. | Cardiac stimulation apparatus and method for the control of hypertension |
| US20060084659A1 (en) * | 2004-10-19 | 2006-04-20 | Michael Davis | Augmentation of psychotherapy with cannabinoid reuptake inhibitors |
| CA2592138A1 (en) * | 2004-12-22 | 2006-06-29 | Warner-Lambert Company Llc | Compositions and methods for expression and purification of fatty acid amide hydrolase |
| US20090068107A1 (en) * | 2006-10-02 | 2009-03-12 | The Scripps Research Institute | Enzyme regulating ether lipid signaling pathways |
| JO3598B1 (ar) | 2006-10-10 | 2020-07-05 | Infinity Discovery Inc | الاحماض والاسترات البورونية كمثبطات اميد هيدروليز الحامض الدهني |
| DK2076508T3 (da) * | 2006-10-18 | 2011-02-21 | Pfizer Prod Inc | Biaryl-ether-urinstof-forbindelser |
| US9796998B2 (en) | 2007-04-09 | 2017-10-24 | Colorado State University Research Foundation | Oxygenase-based biosensing systems for measurement of halogenated alkene concentrations |
| CA2702468A1 (en) | 2007-10-12 | 2009-04-23 | University Of Connecticut | Therapeutic applications of fatty acid amide hydrolase inhibitors |
| TW201000107A (en) * | 2008-04-09 | 2010-01-01 | Infinity Pharmaceuticals Inc | Inhibitors of fatty acid amide hydrolase |
| CA2757622A1 (en) | 2009-04-07 | 2010-10-14 | Infinity Pharmaceuticals, Inc. | Inhibitors of fatty acid amide hydrolase |
| WO2010118155A1 (en) | 2009-04-07 | 2010-10-14 | Infinity Pharmaceuticals, Inc. | Inhibitors of fatty acid amide hydrolase |
| US9062116B2 (en) | 2009-04-23 | 2015-06-23 | Infinity Pharmaceuticals, Inc. | Anti-fatty acid amide hydrolase-2 antibodies and uses thereof |
| US8927551B2 (en) * | 2009-05-18 | 2015-01-06 | Infinity Pharmaceuticals, Inc. | Isoxazolines as inhibitors of fatty acid amide hydrolase |
| US8765735B2 (en) * | 2009-05-18 | 2014-07-01 | Infinity Pharmaceuticals, Inc. | Isoxazolines as inhibitors of fatty acid amide hydrolase |
| US9149465B2 (en) * | 2009-05-18 | 2015-10-06 | Infinity Pharmaceuticals, Inc. | Isoxazolines as inhibitors of fatty acid amide hydrolase |
| MX361692B (es) | 2010-02-03 | 2018-12-13 | Infinity Pharmaceuticals Inc | Inhibidores de amida hidrolasa de ácido graso. |
| JP2013147430A (ja) * | 2010-04-28 | 2013-08-01 | Astellas Pharma Inc | 夜間頻尿の予防又は治療剤 |
| TW201206440A (en) * | 2010-04-28 | 2012-02-16 | Astellas Pharma Inc | Prophylactic or therapeutic agent for diseases associated with pains in urinary organs |
| CN103153946B (zh) | 2010-07-28 | 2015-11-25 | 加利福尼亚大学董事会 | 外周限制性 faah 抑制剂 |
| WO2012071471A2 (en) | 2010-11-22 | 2012-05-31 | Colorado State University Research Foundation | Biosensing systems for measurement of lactose |
| US9499853B2 (en) | 2011-08-02 | 2016-11-22 | Colorado State University Research Foundation | Biosensing system with extended lifetime via cofactor recycling |
| WO2013028570A2 (en) | 2011-08-19 | 2013-02-28 | The Regents Of The University Of California | Meta-substituted biphenyl peripherally restricted faah inhibitors |
| EP2931291B1 (en) | 2012-12-11 | 2021-10-20 | The McLean Hospital Corporation | Xenon treatment as an adjunct to psychotherapy for psychiatric disorders |
| US9008769B2 (en) | 2012-12-21 | 2015-04-14 | Backbeat Medical, Inc. | Methods and systems for lowering blood pressure through reduction of ventricle filling |
| MX372678B (es) | 2012-12-28 | 2020-03-25 | Rohm & Haas | Adhesivos hidrosolubles. |
| CN104884425B (zh) * | 2012-12-28 | 2017-11-10 | 罗门哈斯公司 | 脂肪酰胺的水性分散液 |
| US9370662B2 (en) | 2013-12-19 | 2016-06-21 | Backbeat Medical, Inc. | Methods and systems for controlling blood pressure by controlling atrial pressure |
| GB201404468D0 (en) * | 2014-03-13 | 2014-04-30 | Givaudan Sa | Process |
| ES2908240T3 (es) | 2014-04-07 | 2022-04-28 | Univ California | Inhibidores de la enzima amida hidrolasa de ácidos grasos (FAAH) con biodisponibilidad oral mejorada y su uso como medicamentos |
| US10342982B2 (en) | 2015-09-11 | 2019-07-09 | Backbeat Medical, Inc. | Methods and systems for treating cardiac malfunction |
| DK3362462T3 (da) | 2015-10-12 | 2021-10-11 | Advanced Cell Diagnostics Inc | In situ-detektion af nukleotidvarianter i prøver med højt støjniveau, og sammensætninger og fremgangsmåder relateret dertil |
| US10485658B2 (en) | 2016-04-22 | 2019-11-26 | Backbeat Medical, Inc. | Methods and systems for controlling blood pressure |
| US11359182B2 (en) | 2017-09-12 | 2022-06-14 | Ginkgo Bioworks, Inc. | Protective enzymes |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4165258A (en) | 1975-10-08 | 1979-08-21 | University Of Pennsylvania | Plasminogen activating enzyme-specific competitive inhibitor |
-
1996
- 1996-11-04 US US08/743,168 patent/US6271015B1/en not_active Expired - Lifetime
-
1997
- 1997-11-04 JP JP52181298A patent/JP4102445B2/ja not_active Expired - Lifetime
- 1997-11-04 AT AT97948210T patent/ATE376055T1/de not_active IP Right Cessation
- 1997-11-04 ES ES97948210T patent/ES2294802T3/es not_active Expired - Lifetime
- 1997-11-04 EP EP97948210A patent/EP0970195B1/en not_active Expired - Lifetime
- 1997-11-04 DE DE69738221T patent/DE69738221T2/de not_active Expired - Lifetime
- 1997-11-04 WO PCT/US1997/020385 patent/WO1998020119A1/en not_active Ceased
- 1997-11-04 DK DK97948210T patent/DK0970195T3/da active
- 1997-11-04 CA CA002270293A patent/CA2270293A1/en not_active Abandoned
- 1997-11-04 AU AU54321/98A patent/AU739962B2/en not_active Expired
-
2001
- 2001-06-28 US US09/894,790 patent/US6699682B2/en not_active Expired - Lifetime
-
2004
- 2004-02-26 US US10/788,992 patent/US7348173B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US7348173B2 (en) | 2008-03-25 |
| US20040265958A1 (en) | 2004-12-30 |
| DK0970195T3 (da) | 2008-02-18 |
| EP0970195A4 (en) | 2001-12-05 |
| JP2001503630A (ja) | 2001-03-21 |
| WO1998020119A1 (en) | 1998-05-14 |
| US20020187542A1 (en) | 2002-12-12 |
| JP4102445B2 (ja) | 2008-06-18 |
| EP0970195B1 (en) | 2007-10-17 |
| CA2270293A1 (en) | 1998-05-14 |
| AU5432198A (en) | 1998-05-29 |
| ATE376055T1 (de) | 2007-11-15 |
| US6271015B1 (en) | 2001-08-07 |
| DE69738221T2 (de) | 2008-07-24 |
| US6699682B2 (en) | 2004-03-02 |
| EP0970195A1 (en) | 2000-01-12 |
| DE69738221D1 (de) | 2007-11-29 |
| AU739962B2 (en) | 2001-10-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2294802T3 (es) | Hidrolasa de amidas de acidos grasos. | |
| Ueno | Enzymatic and structural aspects on glutamate decarboxylase | |
| WO1998020119A9 (en) | Fatty-acid amide hydrolase | |
| Reichel et al. | Molecular cloning and expression of a 2-arylpropionyl-coenzyme A epimerase: a key enzyme in the inversion metabolism of ibuprofen | |
| PT673426E (pt) | Acetil-hidrolase do factor activador das plaquetas | |
| AU712759B2 (en) | TNF-alpha converting enzyme | |
| CA2132982C (en) | Catalytic antibodies against cocaine and methods of using and producing same | |
| US20040241795A1 (en) | Compounds and methods for inhibiting axillary malodour | |
| US5519163A (en) | Inhibitors of phosphoinositide-specific phospholipase C | |
| CA1299508C (en) | Human pancreatic elastase i | |
| CA2183253A1 (en) | Rna editing enzyme and methods of use thereof | |
| EP0833899B1 (en) | Cis-9,10-octadecenoamidase | |
| AU781382B2 (en) | Fatty-acid amide hydrolase | |
| FI95928B (fi) | Molekyylit, joissa on vasta-ainetta liittävät kohdat ja joilla on stereospesifinen katalyysi | |
| US10544421B1 (en) | System and method for creating crystals of human acetylcholinesterase with open active sites | |
| Fiordalisi | Molecular cloning and functional analysis of the murine interleukin-1-beta converting enzyme | |
| Mueller | LEUKOTRIENE A4 HYDROLASE | |
| JP2001333776A (ja) | ヒト由来プロテインホスファターゼ及びその阻害化合物 | |
| Mueller | Leukotriene A4 hydrolase: identification of amino acid residues involved in catalyses and substrate-mediated inactivation | |
| Bai | Cloning and expressing alternatively spliced PI-PLC beta 1 | |
| Patricelli | Biochemical and physiological investigations of fatty acid amide hydrolase | |
| JPWO2003031628A1 (ja) | スフィンゴシンキナーゼ活性を有する分泌型ポリペプチドおよびそれをコードするスフィンゴシンキナーゼ遺伝子 |