JP2000506392A - 新規なヒト代謝指向型グルタミン酸レセプター - Google Patents
新規なヒト代謝指向型グルタミン酸レセプターInfo
- Publication number
- JP2000506392A JP2000506392A JP9540300A JP54030097A JP2000506392A JP 2000506392 A JP2000506392 A JP 2000506392A JP 9540300 A JP9540300 A JP 9540300A JP 54030097 A JP54030097 A JP 54030097A JP 2000506392 A JP2000506392 A JP 2000506392A
- Authority
- JP
- Japan
- Prior art keywords
- nucleic acid
- seq
- receptor
- sequence
- metabotropic glutamate
- 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.)
- Pending
Links
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 title claims abstract description 328
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 title claims abstract description 328
- 241000282414 Homo sapiens Species 0.000 title claims abstract description 67
- 102000005962 receptors Human genes 0.000 claims abstract description 212
- 108020003175 receptors Proteins 0.000 claims abstract description 209
- 230000000694 effects Effects 0.000 claims abstract description 164
- 150000001875 compounds Chemical class 0.000 claims abstract description 96
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 59
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 34
- 208000012902 Nervous system disease Diseases 0.000 claims abstract description 19
- 208000025966 Neurological disease Diseases 0.000 claims abstract description 13
- 238000012216 screening Methods 0.000 claims abstract description 11
- 150000007523 nucleic acids Chemical class 0.000 claims description 219
- 102000039446 nucleic acids Human genes 0.000 claims description 170
- 108020004707 nucleic acids Proteins 0.000 claims description 170
- 210000004027 cell Anatomy 0.000 claims description 144
- 238000000034 method Methods 0.000 claims description 115
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 78
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 75
- 229920001184 polypeptide Polymers 0.000 claims description 70
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 67
- 239000002773 nucleotide Substances 0.000 claims description 67
- 125000003729 nucleotide group Chemical group 0.000 claims description 67
- 150000001413 amino acids Chemical class 0.000 claims description 66
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 65
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 56
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 50
- 102000018899 Glutamate Receptors Human genes 0.000 claims description 47
- 108010027915 Glutamate Receptors Proteins 0.000 claims description 47
- 108020004414 DNA Proteins 0.000 claims description 45
- 229930195712 glutamate Natural products 0.000 claims description 43
- 239000000556 agonist Substances 0.000 claims description 42
- 201000010099 disease Diseases 0.000 claims description 38
- 230000003834 intracellular effect Effects 0.000 claims description 36
- 230000014509 gene expression Effects 0.000 claims description 32
- 230000027455 binding Effects 0.000 claims description 25
- 239000011230 binding agent Substances 0.000 claims description 25
- 239000002299 complementary DNA Substances 0.000 claims description 25
- 230000000295 complement effect Effects 0.000 claims description 23
- 239000013604 expression vector Substances 0.000 claims description 21
- 230000015572 biosynthetic process Effects 0.000 claims description 20
- 230000002503 metabolic effect Effects 0.000 claims description 20
- 239000005557 antagonist Substances 0.000 claims description 18
- 239000011575 calcium Substances 0.000 claims description 18
- 230000009261 transgenic effect Effects 0.000 claims description 18
- 230000001965 increasing effect Effects 0.000 claims description 17
- 108700010039 chimeric receptor Proteins 0.000 claims description 16
- 125000000539 amino acid group Chemical group 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 229910052791 calcium Inorganic materials 0.000 claims description 13
- 239000003053 toxin Substances 0.000 claims description 13
- 231100000765 toxin Toxicity 0.000 claims description 13
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 12
- 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 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 12
- 230000007062 hydrolysis Effects 0.000 claims description 11
- 238000006460 hydrolysis reaction Methods 0.000 claims description 11
- 238000001727 in vivo Methods 0.000 claims description 11
- 102000030621 adenylate cyclase Human genes 0.000 claims description 10
- 108060000200 adenylate cyclase Proteins 0.000 claims description 10
- 238000000338 in vitro Methods 0.000 claims description 10
- 206010010904 Convulsion Diseases 0.000 claims description 9
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 9
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 8
- 230000004770 neurodegeneration Effects 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 7
- 206010019196 Head injury Diseases 0.000 claims description 6
- 229940114079 arachidonic acid Drugs 0.000 claims description 6
- 235000021342 arachidonic acid Nutrition 0.000 claims description 6
- 230000006378 damage Effects 0.000 claims description 6
- 230000001766 physiological effect Effects 0.000 claims description 6
- 230000001105 regulatory effect Effects 0.000 claims description 6
- 230000003213 activating effect Effects 0.000 claims description 5
- 206010015037 epilepsy Diseases 0.000 claims description 5
- 230000000302 ischemic effect Effects 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000016988 Hemorrhagic Stroke Diseases 0.000 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- 206010021143 Hypoxia Diseases 0.000 claims description 4
- 208000032382 Ischaemic stroke Diseases 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- 102000014384 Type C Phospholipases Human genes 0.000 claims description 4
- 108010079194 Type C Phospholipases Proteins 0.000 claims description 4
- 239000000872 buffer Substances 0.000 claims description 4
- 208000014674 injury Diseases 0.000 claims description 4
- 208000020658 intracerebral hemorrhage Diseases 0.000 claims description 4
- 208000020431 spinal cord injury Diseases 0.000 claims description 4
- 108010078321 Guanylate Cyclase Proteins 0.000 claims description 3
- 102000014469 Guanylate cyclase Human genes 0.000 claims description 3
- 102000004257 Potassium Channel Human genes 0.000 claims description 3
- 208000027418 Wounds and injury Diseases 0.000 claims description 3
- 230000033228 biological regulation Effects 0.000 claims description 3
- 230000001086 cytosolic effect Effects 0.000 claims description 3
- 230000003247 decreasing effect Effects 0.000 claims description 3
- 230000007954 hypoxia Effects 0.000 claims description 3
- 230000001537 neural effect Effects 0.000 claims description 3
- 150000003906 phosphoinositides Chemical class 0.000 claims description 3
- 108020001213 potassium channel Proteins 0.000 claims description 3
- 230000011514 reflex Effects 0.000 claims description 3
- 102000003839 Human Proteins Human genes 0.000 claims description 2
- 108090000144 Human Proteins Proteins 0.000 claims description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 claims description 2
- 229940125516 allosteric modulator Drugs 0.000 claims description 2
- 230000037007 arousal Effects 0.000 claims description 2
- 238000012875 competitive assay Methods 0.000 claims description 2
- 230000003492 excitotoxic effect Effects 0.000 claims description 2
- 150000002306 glutamic acid derivatives Chemical class 0.000 claims description 2
- 238000012544 monitoring process Methods 0.000 claims description 2
- 230000007472 neurodevelopment Effects 0.000 claims description 2
- 230000016273 neuron death Effects 0.000 claims description 2
- 230000004112 neuroprotection Effects 0.000 claims description 2
- 230000001720 vestibular Effects 0.000 claims description 2
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 claims 1
- 108090000312 Calcium Channels Proteins 0.000 claims 1
- 102000003922 Calcium Channels Human genes 0.000 claims 1
- 230000000747 cardiac effect Effects 0.000 claims 1
- 230000036461 convulsion Effects 0.000 claims 1
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 claims 1
- 231100000063 excitotoxicity Toxicity 0.000 claims 1
- 230000003278 mimic effect Effects 0.000 claims 1
- 235000016709 nutrition Nutrition 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 15
- 238000003745 diagnosis Methods 0.000 abstract description 6
- 235000001014 amino acid Nutrition 0.000 description 68
- 229940024606 amino acid Drugs 0.000 description 67
- 239000012634 fragment Substances 0.000 description 67
- 230000004913 activation Effects 0.000 description 55
- 229940049906 glutamate Drugs 0.000 description 41
- 238000003752 polymerase chain reaction Methods 0.000 description 39
- 238000009396 hybridization Methods 0.000 description 32
- 235000018102 proteins Nutrition 0.000 description 31
- 239000002253 acid Substances 0.000 description 30
- 210000002569 neuron Anatomy 0.000 description 29
- 241001465754 Metazoa Species 0.000 description 28
- 239000000047 product Substances 0.000 description 26
- 239000000523 sample Substances 0.000 description 25
- 239000003814 drug Substances 0.000 description 24
- 238000003556 assay Methods 0.000 description 23
- 239000000203 mixture Substances 0.000 description 22
- 108020004999 messenger RNA Proteins 0.000 description 21
- 210000000287 oocyte Anatomy 0.000 description 20
- 101001027295 Homo sapiens Metabotropic glutamate receptor 8 Proteins 0.000 description 19
- 210000001519 tissue Anatomy 0.000 description 19
- 208000035475 disorder Diseases 0.000 description 18
- 229940079593 drug Drugs 0.000 description 18
- 229960002989 glutamic acid Drugs 0.000 description 18
- 102000053642 Catalytic RNA Human genes 0.000 description 17
- 108090000994 Catalytic RNA Proteins 0.000 description 17
- 108091092562 ribozyme Proteins 0.000 description 17
- 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 16
- 210000003169 central nervous system Anatomy 0.000 description 16
- 108091034117 Oligonucleotide Proteins 0.000 description 15
- 239000012528 membrane Substances 0.000 description 15
- 230000006870 function Effects 0.000 description 14
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 13
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 13
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 13
- 101001027296 Mus musculus Metabotropic glutamate receptor 8 Proteins 0.000 description 13
- 241000700159 Rattus Species 0.000 description 13
- 235000013922 glutamic acid Nutrition 0.000 description 13
- 239000004220 glutamic acid Substances 0.000 description 13
- 230000008569 process Effects 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
- 230000007423 decrease Effects 0.000 description 12
- 230000004048 modification Effects 0.000 description 12
- 238000012986 modification Methods 0.000 description 12
- 230000003518 presynaptic effect Effects 0.000 description 12
- 108700012359 toxins Proteins 0.000 description 12
- YFYNOWXBIBKGHB-FBCQKBJTSA-N (1s,3r)-1-aminocyclopentane-1,3-dicarboxylic acid Chemical compound OC(=O)[C@]1(N)CC[C@@H](C(O)=O)C1 YFYNOWXBIBKGHB-FBCQKBJTSA-N 0.000 description 11
- 102000013830 Calcium-Sensing Receptors Human genes 0.000 description 11
- 108010050543 Calcium-Sensing Receptors Proteins 0.000 description 11
- 101100043639 Glycine max ACPD gene Proteins 0.000 description 11
- ASNFTDCKZKHJSW-REOHCLBHSA-N Quisqualic acid Chemical compound OC(=O)[C@@H](N)CN1OC(=O)NC1=O ASNFTDCKZKHJSW-REOHCLBHSA-N 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- 239000013612 plasmid Substances 0.000 description 11
- 238000001890 transfection Methods 0.000 description 11
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 10
- 230000002159 abnormal effect Effects 0.000 description 10
- 239000000074 antisense oligonucleotide Substances 0.000 description 10
- 238000012230 antisense oligonucleotides Methods 0.000 description 10
- 210000004899 c-terminal region Anatomy 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 239000013598 vector Substances 0.000 description 10
- 102100037636 Metabotropic glutamate receptor 8 Human genes 0.000 description 9
- 241000269370 Xenopus <genus> Species 0.000 description 9
- 230000003321 amplification Effects 0.000 description 9
- 238000003776 cleavage reaction Methods 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 108010038448 metabotropic glutamate receptor 8 Proteins 0.000 description 9
- 238000003199 nucleic acid amplification method Methods 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 230000007017 scission Effects 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 238000010561 standard procedure Methods 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- DDOQBQRIEWHWBT-VKHMYHEASA-N (2S)-2-amino-4-phosphonobutanoic acid Chemical compound OC(=O)[C@@H](N)CCP(O)(O)=O DDOQBQRIEWHWBT-VKHMYHEASA-N 0.000 description 8
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- 108090000862 Ion Channels Proteins 0.000 description 8
- 102000004310 Ion Channels Human genes 0.000 description 8
- VJBCNMFKFZIXHC-UHFFFAOYSA-N azanium;2-(4-methyl-5-oxo-4-propan-2-yl-1h-imidazol-2-yl)quinoline-3-carboxylate Chemical compound N.N1C(=O)C(C(C)C)(C)N=C1C1=NC2=CC=CC=C2C=C1C(O)=O VJBCNMFKFZIXHC-UHFFFAOYSA-N 0.000 description 8
- 239000003446 ligand Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 108700019146 Transgenes Proteins 0.000 description 7
- 230000009471 action Effects 0.000 description 7
- 238000007792 addition Methods 0.000 description 7
- 230000000202 analgesic effect Effects 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000000692 anti-sense effect Effects 0.000 description 7
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 7
- 238000010367 cloning Methods 0.000 description 7
- 238000013461 design Methods 0.000 description 7
- 235000004554 glutamine Nutrition 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 210000004940 nucleus Anatomy 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 238000011160 research Methods 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 230000008685 targeting Effects 0.000 description 7
- 238000012546 transfer Methods 0.000 description 7
- ASNFTDCKZKHJSW-UHFFFAOYSA-N DL-Quisqualic acid Natural products OC(=O)C(N)CN1OC(=O)NC1=O ASNFTDCKZKHJSW-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 6
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 6
- GZOVEPYOCJWRFC-UHFFFAOYSA-N L-trans-alpha-Amino-2-carboxycyclopropaneacetic acid Chemical compound OC(=O)C(N)C1CC1C(O)=O GZOVEPYOCJWRFC-UHFFFAOYSA-N 0.000 description 6
- 208000002193 Pain Diseases 0.000 description 6
- 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 6
- -1 aliphatic amino acid Chemical class 0.000 description 6
- 230000036755 cellular response Effects 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 238000010369 molecular cloning Methods 0.000 description 6
- 230000035772 mutation Effects 0.000 description 6
- 241000283690 Bos taurus Species 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 108091026890 Coding region Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 241000720950 Gluta Species 0.000 description 5
- 102100036834 Metabotropic glutamate receptor 1 Human genes 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 5
- 108010081690 Pertussis Toxin Proteins 0.000 description 5
- 108090000631 Trypsin Proteins 0.000 description 5
- 102000004142 Trypsin Human genes 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 230000001593 cAMP accumulation Effects 0.000 description 5
- 210000003710 cerebral cortex Anatomy 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000002950 deficient Effects 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 210000002257 embryonic structure Anatomy 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 239000003292 glue Substances 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 210000004962 mammalian cell Anatomy 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- 108010014719 metabotropic glutamate receptor type 1 Proteins 0.000 description 5
- 108020004083 metabotropic receptors Proteins 0.000 description 5
- 230000000324 neuroprotective effect Effects 0.000 description 5
- 230000003957 neurotransmitter release Effects 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 230000036407 pain Effects 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 239000010452 phosphate Substances 0.000 description 5
- 230000001242 postsynaptic effect Effects 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 239000012588 trypsin Substances 0.000 description 5
- 229960001322 trypsin Drugs 0.000 description 5
- 102000053602 DNA Human genes 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
- 108091006027 G proteins Proteins 0.000 description 4
- 102000030782 GTP binding Human genes 0.000 description 4
- 108091000058 GTP-Binding Proteins 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 4
- VLSMHEGGTFMBBZ-OOZYFLPDSA-M Kainate Chemical compound CC(=C)[C@H]1C[NH2+][C@H](C([O-])=O)[C@H]1CC([O-])=O VLSMHEGGTFMBBZ-OOZYFLPDSA-M 0.000 description 4
- 102100038294 Metabotropic glutamate receptor 7 Human genes 0.000 description 4
- 239000012124 Opti-MEM Substances 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 230000003281 allosteric effect Effects 0.000 description 4
- 230000001773 anti-convulsant effect Effects 0.000 description 4
- 108010058966 bacteriophage T7 induced DNA polymerase Proteins 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 210000000349 chromosome Anatomy 0.000 description 4
- ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 4
- 230000002964 excitative effect Effects 0.000 description 4
- 210000001320 hippocampus Anatomy 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 230000001976 improved effect Effects 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 108010038449 metabotropic glutamate receptor 7 Proteins 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 230000001991 pathophysiological effect Effects 0.000 description 4
- 208000033808 peripheral neuropathy Diseases 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
- 230000000704 physical effect Effects 0.000 description 4
- 238000000159 protein binding assay Methods 0.000 description 4
- 238000007423 screening assay Methods 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000972773 Aulopiformes Species 0.000 description 3
- 108091033380 Coding strand Proteins 0.000 description 3
- 238000001712 DNA sequencing Methods 0.000 description 3
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 3
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 208000004454 Hyperalgesia Diseases 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 description 3
- 102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 description 3
- 102100038357 Metabotropic glutamate receptor 5 Human genes 0.000 description 3
- 102100038300 Metabotropic glutamate receptor 6 Human genes 0.000 description 3
- 108700026244 Open Reading Frames Proteins 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 238000012300 Sequence Analysis Methods 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 229960003767 alanine Drugs 0.000 description 3
- 230000004075 alteration Effects 0.000 description 3
- 239000001961 anticonvulsive agent Substances 0.000 description 3
- 229960003965 antiepileptics Drugs 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 description 3
- 235000011010 calcium phosphates Nutrition 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 210000001638 cerebellum Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000037411 cognitive enhancing Effects 0.000 description 3
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 3
- 108091036078 conserved sequence Proteins 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- MATPZHBYOVDBLI-JJYYJPOSSA-N dcg-iv Chemical compound OC(=O)[C@@H](N)C1[C@@H](C(O)=O)[C@@H]1C(O)=O MATPZHBYOVDBLI-JJYYJPOSSA-N 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 235000013601 eggs Nutrition 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 230000009540 excitatory neurotransmission Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000005714 functional activity Effects 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 238000002744 homologous recombination Methods 0.000 description 3
- 230000006801 homologous recombination Effects 0.000 description 3
- 210000004408 hybridoma Anatomy 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 108010038421 metabotropic glutamate receptor 2 Proteins 0.000 description 3
- 108010038450 metabotropic glutamate receptor 6 Proteins 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 210000001577 neostriatum Anatomy 0.000 description 3
- 230000003961 neuronal insult Effects 0.000 description 3
- 201000001119 neuropathy Diseases 0.000 description 3
- 230000007823 neuropathy Effects 0.000 description 3
- 210000000956 olfactory bulb Anatomy 0.000 description 3
- 230000035778 pathophysiological process Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 210000001236 prokaryotic cell Anatomy 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 235000019515 salmon Nutrition 0.000 description 3
- 238000002741 site-directed mutagenesis Methods 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 230000005062 synaptic transmission Effects 0.000 description 3
- 235000019640 taste Nutrition 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 210000004885 white matter Anatomy 0.000 description 3
- 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 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- IRJCBFDCFXCWGO-SCSAIBSYSA-N (2r)-2-azaniumyl-2-(3-oxo-1,2-oxazol-5-yl)acetate Chemical compound [O-]C(=O)[C@H]([NH3+])C1=CC(=O)NO1 IRJCBFDCFXCWGO-SCSAIBSYSA-N 0.000 description 2
- BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 description 2
- NPDBDJFLKKQMCM-SCSAIBSYSA-N (2s)-2-amino-3,3-dimethylbutanoic acid Chemical compound CC(C)(C)[C@H](N)C(O)=O NPDBDJFLKKQMCM-SCSAIBSYSA-N 0.000 description 2
- AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical class O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 description 2
- DNCAZYRLRMTVSF-JTQLQIEISA-N (S)-alpha-methyl-4-carboxyphenylglycine Chemical compound OC(=O)[C@](N)(C)C1=CC=C(C(O)=O)C=C1 DNCAZYRLRMTVSF-JTQLQIEISA-N 0.000 description 2
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 208000034172 Autoimmune Experimental Myasthenia Gravis Diseases 0.000 description 2
- 241000271566 Aves Species 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 108091006146 Channels Proteins 0.000 description 2
- 108090000317 Chymotrypsin Proteins 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 108010017826 DNA Polymerase I Proteins 0.000 description 2
- 102000004594 DNA Polymerase I Human genes 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 108010042407 Endonucleases Proteins 0.000 description 2
- 102000004533 Endonucleases Human genes 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical group O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
- 208000035154 Hyperesthesia Diseases 0.000 description 2
- IRJCBFDCFXCWGO-UHFFFAOYSA-N Ibotenic acid Natural products OC(=O)C(N)C1=CC(=O)NO1 IRJCBFDCFXCWGO-UHFFFAOYSA-N 0.000 description 2
- 102000009855 Inwardly Rectifying Potassium Channels Human genes 0.000 description 2
- 108010009983 Inwardly Rectifying Potassium Channels Proteins 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical compound C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 2
- QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Natural products CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 2
- 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 2
- 102100038354 Metabotropic glutamate receptor 4 Human genes 0.000 description 2
- 108010085220 Multiprotein Complexes Proteins 0.000 description 2
- 102000007474 Multiprotein Complexes Human genes 0.000 description 2
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 2
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 2
- 229930193140 Neomycin Natural products 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- 108090000284 Pepsin A Proteins 0.000 description 2
- 102000057297 Pepsin A Human genes 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 101001071458 Rattus norvegicus Metabotropic glutamate receptor 2 Proteins 0.000 description 2
- 101001032854 Rattus norvegicus Metabotropic glutamate receptor 4 Proteins 0.000 description 2
- 101001032842 Rattus norvegicus Metabotropic glutamate receptor 6 Proteins 0.000 description 2
- 101001032835 Rattus norvegicus Metabotropic glutamate receptor 7 Proteins 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 101100221606 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) COS7 gene Proteins 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- 241000282887 Suidae Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 101710137500 T7 RNA polymerase Proteins 0.000 description 2
- 108091036066 Three prime untranslated region Proteins 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 238000000376 autoradiography Methods 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 238000010256 biochemical assay Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 210000002459 blastocyst Anatomy 0.000 description 2
- 230000003491 cAMP production Effects 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229960002376 chymotrypsin Drugs 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 239000000562 conjugate Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000001351 cycling effect Effects 0.000 description 2
- XVOYSCVBGLVSOL-UHFFFAOYSA-N cysteic acid Chemical compound OC(=O)C(N)CS(O)(=O)=O XVOYSCVBGLVSOL-UHFFFAOYSA-N 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 210000002308 embryonic cell Anatomy 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 239000003823 glutamate receptor agonist Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 description 2
- 238000013537 high throughput screening Methods 0.000 description 2
- 230000002267 hypothalamic effect Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 239000002596 immunotoxin Substances 0.000 description 2
- 230000002637 immunotoxin Effects 0.000 description 2
- 231100000608 immunotoxin Toxicity 0.000 description 2
- 229940051026 immunotoxin Drugs 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 229910001410 inorganic ion Inorganic materials 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 235000014705 isoleucine Nutrition 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 150000002611 lead compounds Chemical class 0.000 description 2
- 229960003136 leucine Drugs 0.000 description 2
- 235000005772 leucine Nutrition 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 210000001161 mammalian embryo Anatomy 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 108010038422 metabotropic glutamate receptor 4 Proteins 0.000 description 2
- 102000006239 metabotropic receptors Human genes 0.000 description 2
- 239000007758 minimum essential medium Substances 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 229960004927 neomycin Drugs 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 208000004296 neuralgia Diseases 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 210000002741 palatine tonsil Anatomy 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229940111202 pepsin Drugs 0.000 description 2
- 210000001428 peripheral nervous system Anatomy 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000006337 proteolytic cleavage Effects 0.000 description 2
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 210000001525 retina Anatomy 0.000 description 2
- 230000002207 retinal effect Effects 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 238000010187 selection method Methods 0.000 description 2
- 235000004400 serine Nutrition 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 238000010532 solid phase synthesis reaction Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000000225 synapse Anatomy 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 229960004295 valine Drugs 0.000 description 2
- 235000014393 valine Nutrition 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- GZOVEPYOCJWRFC-HZLVTQRSSA-N (1s,2s)-2-[(s)-amino(carboxy)methyl]cyclopropane-1-carboxylic acid Chemical compound OC(=O)[C@@H](N)[C@H]1C[C@@H]1C(O)=O GZOVEPYOCJWRFC-HZLVTQRSSA-N 0.000 description 1
- MRTPISKDZDHEQI-YFKPBYRVSA-N (2s)-2-(tert-butylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC(C)(C)C MRTPISKDZDHEQI-YFKPBYRVSA-N 0.000 description 1
- DQLYTFPAEVJTFM-ZETCQYMHSA-N (2s)-2-azaniumyl-2-(3-hydroxyphenyl)acetate Chemical compound OC(=O)[C@@H](N)C1=CC=CC(O)=C1 DQLYTFPAEVJTFM-ZETCQYMHSA-N 0.000 description 1
- HOOWCUZPEFNHDT-ZETCQYMHSA-N (S)-3,5-dihydroxyphenylglycine Chemical compound OC(=O)[C@@H](N)C1=CC(O)=CC(O)=C1 HOOWCUZPEFNHDT-ZETCQYMHSA-N 0.000 description 1
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
- XYEHOPUEDHAEML-UHFFFAOYSA-N 2-(n-carboxyanilino)propanoic acid Chemical compound OC(=O)C(C)N(C(O)=O)C1=CC=CC=C1 XYEHOPUEDHAEML-UHFFFAOYSA-N 0.000 description 1
- 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 1
- OTLLEIBWKHEHGU-UHFFFAOYSA-N 2-[5-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-4-phosphonooxyhexanedioic acid Chemical compound C1=NC=2C(N)=NC=NC=2N1C(C(C1O)O)OC1COC1C(CO)OC(OC(C(O)C(OP(O)(O)=O)C(O)C(O)=O)C(O)=O)C(O)C1O OTLLEIBWKHEHGU-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
- SNBCLPGEMZEWLU-QXFUBDJGSA-N 2-chloro-n-[[(2r,3s,5r)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl]acetamide Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CNC(=O)CCl)[C@@H](O)C1 SNBCLPGEMZEWLU-QXFUBDJGSA-N 0.000 description 1
- GXZSAQLJWLCLOX-ZETCQYMHSA-N 4-[(s)-amino(carboxy)methyl]-2-hydroxybenzoic acid Chemical compound OC(=O)[C@@H](N)C1=CC=C(C(O)=O)C(O)=C1 GXZSAQLJWLCLOX-ZETCQYMHSA-N 0.000 description 1
- VTMJKPGFERYGJF-ZETCQYMHSA-N 4-[(s)-amino(carboxy)methyl]benzoic acid Chemical compound OC(=O)[C@@H](N)C1=CC=C(C(O)=O)C=C1 VTMJKPGFERYGJF-ZETCQYMHSA-N 0.000 description 1
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- 108010005456 AMPA 4 glutamate receptor ionotropic Proteins 0.000 description 1
- 108090000078 AMPA Receptors Proteins 0.000 description 1
- 102000003678 AMPA Receptors Human genes 0.000 description 1
- 108010066676 Abrin Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 241001514645 Agonis Species 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 102000015404 Amino Acid Receptors Human genes 0.000 description 1
- 108010025177 Amino Acid Receptors Proteins 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108010032595 Antibody Binding Sites Proteins 0.000 description 1
- 101100166588 Arabidopsis thaliana CCX1 gene Proteins 0.000 description 1
- 101100041595 Arabidopsis thaliana IREG3 gene Proteins 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 102100039339 Atrial natriuretic peptide receptor 1 Human genes 0.000 description 1
- 101710102163 Atrial natriuretic peptide receptor 1 Proteins 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 231100000699 Bacterial toxin Toxicity 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 208000001387 Causalgia Diseases 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 description 1
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 1
- 208000033001 Complex partial seizures Diseases 0.000 description 1
- 108010060123 Conjugate Vaccines Proteins 0.000 description 1
- AAWZDTNXLSGCEK-UHFFFAOYSA-N Cordycepinsaeure Natural products OC1CC(O)(C(O)=O)CC(O)C1O AAWZDTNXLSGCEK-UHFFFAOYSA-N 0.000 description 1
- 101710095468 Cyclase Proteins 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 239000003298 DNA probe Substances 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010049119 Emotional distress Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 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
- 102100030668 Glutamate receptor 4 Human genes 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001071437 Homo sapiens Metabotropic glutamate receptor 1 Proteins 0.000 description 1
- 101001032841 Homo sapiens Metabotropic glutamate receptor 7 Proteins 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 150000008539 L-glutamic acids Chemical class 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 102100037611 Lysophospholipase Human genes 0.000 description 1
- 241000288147 Meleagris gallopavo Species 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- NPPQSCRMBWNHMW-UHFFFAOYSA-N Meprobamate Chemical compound NC(=O)OCC(C)(CCC)COC(N)=O NPPQSCRMBWNHMW-UHFFFAOYSA-N 0.000 description 1
- 102100038352 Metabotropic glutamate receptor 3 Human genes 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 238000005713 Midland reduction reaction Methods 0.000 description 1
- 241000087624 Monoclona Species 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000016979 Other receptors Human genes 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 208000037158 Partial Epilepsies Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 208000004983 Phantom Limb Diseases 0.000 description 1
- 206010056238 Phantom pain Diseases 0.000 description 1
- 102000011420 Phospholipase D Human genes 0.000 description 1
- 108090000553 Phospholipase D Proteins 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010058864 Phospholipases A2 Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 108091036407 Polyadenylation Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 1
- 102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 1
- AAWZDTNXLSGCEK-ZHQZDSKASA-N Quinic acid Natural products O[C@H]1CC(O)(C(O)=O)C[C@H](O)C1O AAWZDTNXLSGCEK-ZHQZDSKASA-N 0.000 description 1
- 101100015376 Rattus norvegicus Gnaz gene Proteins 0.000 description 1
- 101001071426 Rattus norvegicus Metabotropic glutamate receptor 1 Proteins 0.000 description 1
- 101001032838 Rattus norvegicus Metabotropic glutamate receptor 5 Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 101100255674 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) RTS3 gene Proteins 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 206010040703 Simple partial seizures Diseases 0.000 description 1
- 241000251131 Sphyrna Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 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
- 108020005038 Terminator Codon Proteins 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 101710162629 Trypsin inhibitor Proteins 0.000 description 1
- 229940122618 Trypsin inhibitor Drugs 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 1
- LNQVTSROQXJCDD-UHFFFAOYSA-N adenosine monophosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(CO)C(OP(O)(O)=O)C1O LNQVTSROQXJCDD-UHFFFAOYSA-N 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 206010053552 allodynia Diseases 0.000 description 1
- 230000008848 allosteric regulation Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 239000003194 amino acid receptor blocking agent Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 210000000776 antibody secreting cell Anatomy 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- DMLAVOWQYNRWNQ-UHFFFAOYSA-N azobenzene Chemical compound C1=CC=CC=C1N=NC1=CC=CC=C1 DMLAVOWQYNRWNQ-UHFFFAOYSA-N 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000000688 bacterial toxin Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 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
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 230000010221 calcium permeability Effects 0.000 description 1
- 230000003185 calcium uptake Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000004640 cellular pathway Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 210000000078 claw Anatomy 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 208000014439 complex regional pain syndrome type 2 Diseases 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 229940031670 conjugate vaccine Drugs 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- UCZUCGRGTXIWLR-UHFFFAOYSA-N cyclohexyl hydrogen sulfate Chemical compound OS(=O)(=O)OC1CCCCC1 UCZUCGRGTXIWLR-UHFFFAOYSA-N 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 210000001787 dendrite Anatomy 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 150000001982 diacylglycerols Chemical class 0.000 description 1
- KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
- 125000005442 diisocyanate group Chemical group 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 230000001037 epileptic effect Effects 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000928 excitatory amino acid agonist Substances 0.000 description 1
- 231100000318 excitotoxic Toxicity 0.000 description 1
- 239000002095 exotoxin Substances 0.000 description 1
- 231100000776 exotoxin Toxicity 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 235000019688 fish Nutrition 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000007421 fluorometric assay Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- IECPWNUMDGFDKC-MZJAQBGESA-N fusidic acid Chemical class O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C(O)=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C IECPWNUMDGFDKC-MZJAQBGESA-N 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000003825 glutamate receptor antagonist Substances 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 150000002309 glutamines Chemical class 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000004565 granule cell Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 1
- 235000013928 guanylic acid Nutrition 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 210000004295 hippocampal neuron Anatomy 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 230000000796 hypoacidity effect Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 230000002687 intercalation Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000006525 intracellular process Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000012804 iterative process Methods 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000013016 learning Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 230000020796 long term synaptic depression Effects 0.000 description 1
- 230000027928 long-term synaptic potentiation Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 229940124807 mGLUR antagonist Drugs 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 108010038445 metabotropic glutamate receptor 3 Proteins 0.000 description 1
- 239000003514 metabotropic receptor agonist Substances 0.000 description 1
- 239000003512 metabotropic receptor antagonist Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000003955 neuronal function Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000003040 nociceptive effect Effects 0.000 description 1
- 108091027963 non-coding RNA Proteins 0.000 description 1
- 102000042567 non-coding RNA Human genes 0.000 description 1
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical group CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002664 nootropic agent Substances 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 210000001743 on-bipolar cell Anatomy 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 210000002990 parathyroid gland Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000004713 phosphodiesters Chemical group 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 238000007781 pre-processing Methods 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 210000000063 presynaptic terminal Anatomy 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 150000003147 proline derivatives Chemical class 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229940005657 pyrophosphoric acid Drugs 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 108700013540 rat Wwc1 Proteins 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 210000003370 receptor cell Anatomy 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 102220240796 rs553605556 Human genes 0.000 description 1
- VGGUKFAVHPGNBF-UHFFFAOYSA-N s-ethyl 2,2,2-trifluoroethanethioate Chemical compound CCSC(=O)C(F)(F)F VGGUKFAVHPGNBF-UHFFFAOYSA-N 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 230000020341 sensory perception of pain Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 208000015891 sexual disease Diseases 0.000 description 1
- 230000035936 sexual power Effects 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000007811 spectroscopic assay Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 210000004281 subthalamic nucleus Anatomy 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 208000001608 teratocarcinoma Diseases 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 235000008521 threonine Nutrition 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 238000012090 tissue culture technique Methods 0.000 description 1
- 235000015961 tonic Nutrition 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 229960000716 tonics Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000031836 visual learning Effects 0.000 description 1
- 102000038650 voltage-gated calcium channel activity Human genes 0.000 description 1
- 108091023044 voltage-gated calcium channel activity Proteins 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70571—Receptors; Cell surface antigens; Cell surface determinants for neuromediators, e.g. serotonin receptor, dopamine receptor
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Psychology (AREA)
- Cell Biology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/604,298 US6084084A (en) | 1996-02-21 | 1996-02-21 | Human metabotropic glutamate receptor |
| US08/604,298 | 1996-02-21 | ||
| PCT/US1997/009025 WO1997048724A2 (en) | 1996-02-21 | 1997-02-20 | Human metabotropic glutamate receptor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2000506392A true JP2000506392A (ja) | 2000-05-30 |
| JP2000506392A5 JP2000506392A5 (enExample) | 2004-11-25 |
Family
ID=24419059
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9540300A Pending JP2000506392A (ja) | 1996-02-21 | 1997-02-20 | 新規なヒト代謝指向型グルタミン酸レセプター |
Country Status (10)
| Country | Link |
|---|---|
| US (3) | US6084084A (enExample) |
| EP (1) | EP0882065B1 (enExample) |
| JP (1) | JP2000506392A (enExample) |
| AT (1) | ATE369385T1 (enExample) |
| AU (1) | AU719841B2 (enExample) |
| CA (1) | CA2246751A1 (enExample) |
| DE (1) | DE69737990T2 (enExample) |
| ES (1) | ES2292193T3 (enExample) |
| IL (2) | IL125711A0 (enExample) |
| WO (1) | WO1997048724A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008516606A (ja) * | 2004-10-14 | 2008-05-22 | カーネギー インスチチューション オブ ワシントン | 神経伝達物質センサーおよびそれを用いる方法 |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5521297A (en) * | 1993-06-04 | 1996-05-28 | Salk Institute Biotechnology/Industrial Associates | Nucleic acids encoding human metabotropic glutamate receptors |
| US5981195A (en) * | 1995-07-26 | 1999-11-09 | Nps Pharmaceuticals, Inc. | Chimeric receptors and methods for identifying compounds active at metabotropic glutamate receptors |
| US6221609B1 (en) * | 1996-07-03 | 2001-04-24 | Eli Lilly And Company | Isolate nucleic acid encoding human MGLUR8 |
| EP1066325A1 (en) * | 1998-04-03 | 2001-01-10 | Nps Pharmaceuticals, Inc. | G-protein fusion receptors and chimeric gaba b? receptors |
| US7262280B1 (en) | 1998-04-03 | 2007-08-28 | Nps Pharmaceuticals, Inc. | G-protein fusion receptors and constructs encoding same |
| EP1662255A3 (en) * | 1998-08-18 | 2006-09-13 | The Johns Hopkins University School Of Medicine | Homer interacting proteins |
| WO2000011204A2 (en) * | 1998-08-18 | 2000-03-02 | The Johns Hopkins University School Of Medicine | Homer interacting proteins |
| CA2341018C (en) * | 1998-08-31 | 2012-07-31 | The Provost Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin | Polypeptides and polynucleotides from coagulase-negative staphylococci |
| US20030166554A1 (en) * | 2001-01-16 | 2003-09-04 | Genset, S.A. | Treatment of CNS disorders using D-amino acid oxidase and D-aspartate oxidase antagonists |
| US20030185754A1 (en) * | 2001-01-16 | 2003-10-02 | Genset, S.A. | Treatment of CNS disorders using D-amino acid oxidase and D-aspartate oxidase antagonists |
| US6620850B2 (en) * | 2001-09-19 | 2003-09-16 | University Of Florida | Materials and methods for treatment of neurological disorders involving overactivation of glutamatergic ionotropic receptors |
| WO2003054167A2 (en) * | 2001-12-20 | 2003-07-03 | Merck & Co., Inc. | Identification of novel polymorphic sites in the human mglur8 gene and uses thereof |
| MXPA04006728A (es) * | 2002-01-10 | 2005-08-19 | Osteotrophin Llc | Tratamiento de desordenes oseos con medicamentos anabolicos esqueleticos. |
| US20060252922A1 (en) * | 2002-12-04 | 2006-11-09 | Macina Roberto A | Compositions, splice variants and methods relating to colon specific genes and proteins |
| US20050186658A1 (en) * | 2003-10-17 | 2005-08-25 | Nps Pharmaceuticals, Inc. | Chimeric metabotropic glutamate receptors and uses thereof |
| WO2005073730A1 (en) * | 2004-01-31 | 2005-08-11 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with human metabotropic glutamate receptor 8 (mglur8) |
| AR059898A1 (es) | 2006-03-15 | 2008-05-07 | Janssen Pharmaceutica Nv | Derivados de 3-ciano-piridona 1,4-disustituida y su uso como moduladores alostericos de los receptores mglur2 |
| US8889950B2 (en) * | 2006-07-28 | 2014-11-18 | The George Washington University | Repression of AtGLR3.2 increases plant biomass |
| US7424876B2 (en) * | 2006-10-06 | 2008-09-16 | Ford Global Technologies, Llc | Pushrod engine with multiple independent lash adjusters for each pushrod |
| TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
| TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
| DK2203439T3 (da) | 2007-09-14 | 2011-04-18 | Ortho Mcneil Janssen Pharm | 1',3'-disubstituerede 4-phenyl-3,4,5,6-tetrahydro-2H,1'H-[1,4']-bipyridinyl-2'-oner |
| CA2707309A1 (en) | 2007-12-18 | 2009-06-25 | Acumen Pharmaceuticals, Inc. | Novel addl receptor polypeptides, polynucleotides and host cells for recombinant production |
| WO2010011404A2 (en) * | 2008-05-20 | 2010-01-28 | Eos Neuroscience, Inc. | Vectors for delivery of light-sensitive proteins and methods of use |
| AU2009289784B2 (en) | 2008-09-02 | 2012-03-22 | Addex Pharma S.A. | 3-azabicyclo[3.1.0]hexyl derivatives as modulators of metabotropic glutamate receptors |
| RU2512283C2 (ru) | 2008-11-28 | 2014-04-10 | Янссен Фармасьютикалз, Инк. | Производные индола и бензоксазина в качестве модуляторов метаботропных глутаматных рецепторов |
| JO2907B1 (en) | 2009-05-12 | 2015-09-15 | اديكس فرما اس ايه | Pyridine derivatives 1, 2, 4 trisolo [4, 3-A] and their uses as positive LLs for 2MGLUR receptors |
| MY153913A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| NZ596053A (en) | 2009-05-12 | 2013-05-31 | Janssen Pharmaceuticals Inc | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| CN103298810B (zh) | 2010-11-08 | 2016-03-16 | 杨森制药公司 | 1,2,4-三唑并[4,3-a]吡啶衍生物及其作为MGLUR2受体的正变构调节剂的用途 |
| ES2536433T3 (es) | 2010-11-08 | 2015-05-25 | Janssen Pharmaceuticals, Inc. | Derivados de 1,2,4-triazolo[4,3-a]piridina y su uso como moduladores alostéricos positivos de receptores mGluR2 |
| EP2661435B1 (en) | 2010-11-08 | 2015-08-19 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
| JO3368B1 (ar) | 2013-06-04 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2 |
| JO3367B1 (ar) | 2013-09-06 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2 |
| EA033889B1 (ru) | 2014-01-21 | 2019-12-05 | Янссен Фармацевтика Нв | Комбинация на основе лиганда sv2a и положительного аллостерического модулятора метаботропного глутаматергического рецептора 2 подтипа |
| HUE045610T2 (hu) | 2014-01-21 | 2020-01-28 | Janssen Pharmaceutica Nv | 2-es altípusú metabotróp glutamáterg receptor pozitív allosztérikus modulátorait vagy ortosztérikus agonistáit tartalmazó kombinációk és alkalmazásuk |
| RU2765242C2 (ru) | 2015-08-07 | 2022-01-27 | Имаджинаб, Инк. | Антигенсвязывающие конструкции против молекул-мишеней |
| WO2018147960A1 (en) | 2017-02-08 | 2018-08-16 | Imaginab, Inc. | Extension sequences for diabodies |
| CA3060443A1 (en) | 2017-04-19 | 2018-10-25 | Board Of Regents, The University Of Texas System | Immune cells expressing engineered antigen receptors |
| EP3755349A4 (en) | 2018-02-21 | 2021-11-17 | Board of Regents, The University of Texas System | PROCESS FOR ACTIVATION AND EXPANSION OF NATURAL KILLER CELLS AND THEIR USES |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1311829A (en) * | 1971-02-20 | 1973-03-28 | Hayashibara Co | Sealsoning of comestibles |
| US4945050A (en) * | 1984-11-13 | 1990-07-31 | Cornell Research Foundation, Inc. | Method for transporting substances into living cells and tissues and apparatus therefor |
| US5177011A (en) * | 1988-08-18 | 1993-01-05 | Calgene, Inc. | Plant elongation factor promoters, coding sequences and uses |
| JP2944721B2 (ja) * | 1990-08-22 | 1999-09-06 | 生化学工業株式会社 | エンドトキシンの測定剤 |
| NZ240921A (en) * | 1990-12-12 | 1994-06-27 | Zymogenetics Inc | G protein coupled glutamate receptor (neurotransmitters), recombinant production |
| ES2218531T3 (es) * | 1991-08-23 | 2004-11-16 | Nps Pharmaceuticals, Inc. | Arilalquilaminas activas sobre los receptores del calcio. |
| ES2256370T3 (es) * | 1991-08-23 | 2006-07-16 | Nps Pharmaceuticals, Inc. | Moleculas activas para el receptor de calcio. |
| IL105587A0 (en) * | 1992-05-08 | 1993-09-22 | Lilly Co Eli | Human metabotropic glutamate receptor and related dna compounds |
| EP0642589A4 (en) * | 1992-05-11 | 1997-05-21 | Ribozyme Pharm Inc | METHOD AND REAGENT TO INHIBIT VIRAL REPLICATION. |
| US6228610B1 (en) * | 1993-09-20 | 2001-05-08 | Novartis Corporation | Human metabotropic glutamate receptor subtypes (hmR4, hmR6, hmR7) and related DNA compounds |
| US6274330B1 (en) * | 1993-12-30 | 2001-08-14 | Zymogenetics, Inc. | L-AP4 sensitive glutamate receptors |
| AU6912594A (en) * | 1994-05-16 | 1995-12-05 | Human Genome Sciences, Inc. | Neurotransmitter transporter |
| US5981195A (en) * | 1995-07-26 | 1999-11-09 | Nps Pharmaceuticals, Inc. | Chimeric receptors and methods for identifying compounds active at metabotropic glutamate receptors |
-
1996
- 1996-02-21 US US08/604,298 patent/US6084084A/en not_active Expired - Fee Related
-
1997
- 1997-02-20 AT AT97933988T patent/ATE369385T1/de not_active IP Right Cessation
- 1997-02-20 EP EP97933988A patent/EP0882065B1/en not_active Expired - Lifetime
- 1997-02-20 IL IL12571197A patent/IL125711A0/xx active IP Right Grant
- 1997-02-20 JP JP9540300A patent/JP2000506392A/ja active Pending
- 1997-02-20 CA CA002246751A patent/CA2246751A1/en not_active Abandoned
- 1997-02-20 DE DE69737990T patent/DE69737990T2/de not_active Expired - Fee Related
- 1997-02-20 WO PCT/US1997/009025 patent/WO1997048724A2/en not_active Ceased
- 1997-02-20 ES ES97933988T patent/ES2292193T3/es not_active Expired - Lifetime
- 1997-02-20 AU AU37156/97A patent/AU719841B2/en not_active Ceased
- 1997-03-24 US US08/823,437 patent/US6051688A/en not_active Expired - Fee Related
- 1997-03-24 US US08/823,110 patent/US6077675A/en not_active Expired - Fee Related
-
1998
- 1998-08-09 IL IL125711A patent/IL125711A/en not_active IP Right Cessation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008516606A (ja) * | 2004-10-14 | 2008-05-22 | カーネギー インスチチューション オブ ワシントン | 神経伝達物質センサーおよびそれを用いる方法 |
| JP2013059335A (ja) * | 2004-10-14 | 2013-04-04 | Carnegie Institution Of Washington | 神経伝達物質センサーおよびそれを用いる方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1997048724A2 (en) | 1997-12-24 |
| US6084084A (en) | 2000-07-04 |
| DE69737990T2 (de) | 2008-09-11 |
| WO1997048724A3 (en) | 1998-03-26 |
| AU3715697A (en) | 1998-01-07 |
| EP0882065A2 (en) | 1998-12-09 |
| AU719841B2 (en) | 2000-05-18 |
| DE69737990D1 (de) | 2007-09-20 |
| ATE369385T1 (de) | 2007-08-15 |
| US6077675A (en) | 2000-06-20 |
| US6051688A (en) | 2000-04-18 |
| IL125711A (en) | 2006-09-05 |
| EP0882065B1 (en) | 2007-08-08 |
| IL125711A0 (en) | 1999-04-11 |
| CA2246751A1 (en) | 1997-12-24 |
| ES2292193T3 (es) | 2008-03-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2000506392A (ja) | 新規なヒト代謝指向型グルタミン酸レセプター | |
| AU710128B2 (en) | Chimeric receptors and methods for identifying compounds active at metabotropic glutamate receptors and the use of such compounds in the treatment of neurological disorders and diseases | |
| JP3851653B2 (ja) | ノッチタンパク質および核酸に基づいた治療および診断方法ならびに組成物 | |
| JP2002514055A (ja) | ガラニンｇａｌｒ３受容体をコードするｄｎａおよびその使用 | |
| JPH11507203A (ja) | 脊椎動物Ｓｅｒｒａｔｅ遺伝子のヌクレオチドおよびタンパク質配列およびそれらに基づく方法 | |
| HUT74247A (en) | Human metabotropic glutamate receptor subtypes (hmr4, hmr6, hmr7) and related dna compounds | |
| JPH10510709A (ja) | 摂食行動を変える方法、該方法に有用な化合物、および視床下部の異型神経ペプチドｙ／ペプチドｙｙ受容体（ｙ５）をコードするｄｎａ | |
| JPH09509314A (ja) | 神経ペプチドｙ／ペプチドｙｙ（ｙ２）受容体をコードした核酸、及び該核酸の使用 | |
| US20010023289A1 (en) | DNA encoding a GABABR2 polypeptide and uses thereof | |
| David-Watine et al. | Cloning, expression and electrophysiological characterization of glycine receptor alpha subunit from zebrafish | |
| US6534287B1 (en) | Human metabotropic glutamate receptor | |
| JP2000515005A (ja) | 代謝調節型ｇａｂａ［ｂ］レセプター、レセプター特異的リガンドおよびそれらの使用 | |
| US20020164702A1 (en) | Novel tyrosine kinase receptors and ligands | |
| WO1999051636A9 (en) | Gaba b receptor | |
| US20050186658A1 (en) | Chimeric metabotropic glutamate receptors and uses thereof | |
| JP2000502246A (ja) | 脊椎動物Ｄｅｌｔｅｘタンパク質、核酸および抗体ならびに関連方法および組成物 | |
| AU750179B2 (en) | Chimeric receptors and methods for identifying compounds active at metabotropic glutamate receptors and the use of such compounds in the treatment of neurological disorders and diseases | |
| US20020156265A1 (en) | DNA encoding a GABABR2 polypeptide and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20040219 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040219 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20060725 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20061024 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20070918 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20071116 |