JP2014144017A5

JP2014144017A5 -

Download PDF

Info

Publication number: JP2014144017A5
Authority: JP; Japan
Prior art keywords: antibody; antigen; seq; lingo; binding fragment
Prior art date: 2014-05-19
Legal status : Withdrawn

Application number

JP2014103293A

Other languages

English (en)

Japanese (ja)

Other versions

JP2014144017A (ja

Filing date

2014-05-19

Publication date

2016-03-03

2014-05-19 Application filed filed Critical

2014-08-14 Publication of JP2014144017A publication Critical patent/JP2014144017A/ja

2016-03-03 Publication of JP2014144017A5 publication Critical patent/JP2014144017A5/ja

Status Withdrawn legal-status Critical Current

Links

108090000765 processed proteins & peptides Proteins 0.000 claims description 489
102000004196 processed proteins & peptides Human genes 0.000 claims description 462
229920001184 polypeptide Polymers 0.000 claims description 451
239000012634 fragment Substances 0.000 claims description 444
230000027455 binding Effects 0.000 claims description 403
239000000427 antigen Substances 0.000 claims description 352
102000036639 antigens Human genes 0.000 claims description 352
108091007433 antigens Proteins 0.000 claims description 352
238000000034 method Methods 0.000 claims description 154
125000003275 alpha amino acid group Chemical group 0.000 claims description 112
108090000623 proteins and genes Proteins 0.000 claims description 106
238000006467 substitution reaction Methods 0.000 claims description 57
102000004169 proteins and genes Human genes 0.000 claims description 55
241001465754 Metazoa Species 0.000 claims description 28
239000013604 expression vector Substances 0.000 claims description 27
238000011282 treatment Methods 0.000 claims description 20
239000003814 drug Substances 0.000 claims description 19
210000003169 central nervous system Anatomy 0.000 claims description 18
201000006417 multiple sclerosis Diseases 0.000 claims description 17
230000006378 damage Effects 0.000 claims description 16
102000004190 Enzymes Human genes 0.000 claims description 14
108090000790 Enzymes Proteins 0.000 claims description 14
210000004556 brain Anatomy 0.000 claims description 14
208000027418 Wounds and injury Diseases 0.000 claims description 13
208000014674 injury Diseases 0.000 claims description 13
238000004519 manufacturing process Methods 0.000 claims description 13
239000003795 chemical substances by application Substances 0.000 claims description 11
230000008685 targeting Effects 0.000 claims description 11
101000981680 Homo sapiens Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 Proteins 0.000 claims description 10
241000700605 Viruses Species 0.000 claims description 9
229940124597 therapeutic agent Drugs 0.000 claims description 8
102000052739 human LINGO1 Human genes 0.000 claims description 7
238000000338 in vitro Methods 0.000 claims description 7
150000002632 lipids Chemical class 0.000 claims description 7
239000000651 prodrug Substances 0.000 claims description 6
229940002612 prodrug Drugs 0.000 claims description 6
238000012258 culturing Methods 0.000 claims description 4
239000000367 immunologic factor Substances 0.000 claims description 3
239000008177 pharmaceutical agent Substances 0.000 claims description 3
208000010038 Ischemic Optic Neuropathy Diseases 0.000 claims description 2
206010030924 Optic ischaemic neuropathy Diseases 0.000 claims description 2
108010003723 Single-Domain Antibodies Proteins 0.000 claims description 2
201000007058 anterior ischemic optic neuropathy Diseases 0.000 claims description 2
108010088365 B6 peptide Proteins 0.000 claims 1
108091033319 polynucleotide Proteins 0.000 description 211
102000040430 polynucleotide Human genes 0.000 description 211
239000002157 polynucleotide Substances 0.000 description 210
235000001014 amino acid Nutrition 0.000 description 134
210000004027 cell Anatomy 0.000 description 101
229940024606 amino acid Drugs 0.000 description 99
239000000203 mixture Substances 0.000 description 92
150000001413 amino acids Chemical class 0.000 description 91
241000282414 Homo sapiens Species 0.000 description 86
101100112922 Candida albicans CDR3 gene Proteins 0.000 description 81
150000007523 nucleic acids Chemical class 0.000 description 71
102100035361 Cerebellar degeneration-related protein 2 Human genes 0.000 description 68
101000737796 Homo sapiens Cerebellar degeneration-related protein 2 Proteins 0.000 description 68
102000039446 nucleic acids Human genes 0.000 description 68
108020004707 nucleic acids Proteins 0.000 description 68
101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 description 66
108010047041 Complementarity Determining Regions Proteins 0.000 description 63
239000013598 vector Substances 0.000 description 62
108060003951 Immunoglobulin Proteins 0.000 description 55
102000018358 immunoglobulin Human genes 0.000 description 55
235000018102 proteins Nutrition 0.000 description 49
108020004414 DNA Proteins 0.000 description 40
210000004248 oligodendroglia Anatomy 0.000 description 35
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 34
230000014509 gene expression Effects 0.000 description 33
239000005557 antagonist Substances 0.000 description 27
230000001404 mediated effect Effects 0.000 description 27
101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 description 24
102100036887 Immunoglobulin heavy variable 1-2 Human genes 0.000 description 24
241000699666 Mus <mouse, genus> Species 0.000 description 22
201000010099 disease Diseases 0.000 description 22
108020001507 fusion proteins Proteins 0.000 description 22
102000037865 fusion proteins Human genes 0.000 description 22
229910052739 hydrogen Inorganic materials 0.000 description 22
210000002569 neuron Anatomy 0.000 description 22
238000010494 dissociation reaction Methods 0.000 description 21
230000005593 dissociations Effects 0.000 description 21
108091032973 (ribonucleotides)n+m Proteins 0.000 description 20
230000005764 inhibitory process Effects 0.000 description 20
239000000047 product Substances 0.000 description 20
229910052720 vanadium Inorganic materials 0.000 description 20
238000012217 deletion Methods 0.000 description 19
230000037430 deletion Effects 0.000 description 19
230000004048 modification Effects 0.000 description 19
238000012986 modification Methods 0.000 description 19
108091026890 Coding region Proteins 0.000 description 18
210000004408 hybridoma Anatomy 0.000 description 18
101001008255 Homo sapiens Immunoglobulin kappa variable 1D-8 Proteins 0.000 description 16
101001047628 Homo sapiens Immunoglobulin kappa variable 2-29 Proteins 0.000 description 16
101001008321 Homo sapiens Immunoglobulin kappa variable 2D-26 Proteins 0.000 description 16
101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 description 16
101001008263 Homo sapiens Immunoglobulin kappa variable 3D-15 Proteins 0.000 description 16
102000008394 Immunoglobulin Fragments Human genes 0.000 description 16
108010021625 Immunoglobulin Fragments Proteins 0.000 description 16
102100022949 Immunoglobulin kappa variable 2-29 Human genes 0.000 description 16
102000007079 Peptide Fragments Human genes 0.000 description 16
108010033276 Peptide Fragments Proteins 0.000 description 16
108010076504 Protein Sorting Signals Proteins 0.000 description 16
125000000539 amino acid group Chemical group 0.000 description 15
230000035772 mutation Effects 0.000 description 15
102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 14
108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 14
238000005516 engineering process Methods 0.000 description 14
230000023105 myelination Effects 0.000 description 14
125000003729 nucleotide group Chemical group 0.000 description 14
229940088598 enzyme Drugs 0.000 description 13
230000006870 function Effects 0.000 description 13
239000002773 nucleotide Substances 0.000 description 13
239000013612 plasmid Substances 0.000 description 13
102000000343 Nogo Receptor 1 Human genes 0.000 description 12
108010041199 Nogo Receptor 1 Proteins 0.000 description 12
238000003556 assay Methods 0.000 description 12
230000015572 biosynthetic process Effects 0.000 description 12
208000035475 disorder Diseases 0.000 description 12
229910052731 fluorine Inorganic materials 0.000 description 12
108020004999 messenger RNA Proteins 0.000 description 12
229910052717 sulfur Inorganic materials 0.000 description 12
102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 11
108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 11
230000004069 differentiation Effects 0.000 description 11
229940079593 drug Drugs 0.000 description 11
230000004927 fusion Effects 0.000 description 11
210000000020 growth cone Anatomy 0.000 description 11
239000003550 marker Substances 0.000 description 11
230000001105 regulatory effect Effects 0.000 description 11
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 10
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical group OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 10
108091028043 Nucleic acid sequence Proteins 0.000 description 10
238000001514 detection method Methods 0.000 description 10
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Chemical group OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 10
238000002560 therapeutic procedure Methods 0.000 description 10
238000013518 transcription Methods 0.000 description 10
230000035897 transcription Effects 0.000 description 10
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical group NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 9
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Chemical group NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 9
239000004472 Lysine Chemical group 0.000 description 9
239000002299 complementary DNA Substances 0.000 description 9
230000000694 effects Effects 0.000 description 9
238000002474 experimental method Methods 0.000 description 9
230000014511 neuron projection development Effects 0.000 description 9
241000894007 species Species 0.000 description 9
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 8
238000002965 ELISA Methods 0.000 description 8
241000588724 Escherichia coli Species 0.000 description 8
241000124008 Mammalia Species 0.000 description 8
241000700159 Rattus Species 0.000 description 8
108020004511 Recombinant DNA Proteins 0.000 description 8
238000002405 diagnostic procedure Methods 0.000 description 8
238000005755 formation reaction Methods 0.000 description 8
230000012010 growth Effects 0.000 description 8
230000002401 inhibitory effect Effects 0.000 description 8
239000000463 material Substances 0.000 description 8
230000008569 process Effects 0.000 description 8
239000000126 substance Substances 0.000 description 8
239000004475 Arginine Substances 0.000 description 7
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 7
108010087819 Fc receptors Proteins 0.000 description 7
102000009109 Fc receptors Human genes 0.000 description 7
108010067060 Immunoglobulin Variable Region Proteins 0.000 description 7
102000017727 Immunoglobulin Variable Region Human genes 0.000 description 7
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 7
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 7
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 7
102000006386 Myelin Proteins Human genes 0.000 description 7
108010083674 Myelin Proteins Proteins 0.000 description 7
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 7
235000009582 asparagine Nutrition 0.000 description 7
229960001230 asparagine Drugs 0.000 description 7
210000003050 axon Anatomy 0.000 description 7
230000000295 complement effect Effects 0.000 description 7
201000002491 encephalomyelitis Diseases 0.000 description 7
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 7
238000002955 isolation Methods 0.000 description 7
239000003446 ligand Substances 0.000 description 7
230000000670 limiting effect Effects 0.000 description 7
210000004962 mammalian cell Anatomy 0.000 description 7
210000005012 myelin Anatomy 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
238000002823 phage display Methods 0.000 description 7
229920001223 polyethylene glycol Polymers 0.000 description 7
238000000746 purification Methods 0.000 description 7
210000002966 serum Anatomy 0.000 description 7
230000002103 transcriptional effect Effects 0.000 description 7
208000016192 Demyelinating disease Diseases 0.000 description 6
206010012305 Demyelination Diseases 0.000 description 6
108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 6
241000699670 Mus sp. Species 0.000 description 6
206010028980 Neoplasm Diseases 0.000 description 6
108700026244 Open Reading Frames Proteins 0.000 description 6
208000017493 Pelizaeus-Merzbacher disease Diseases 0.000 description 6
238000007792 addition Methods 0.000 description 6
230000003302 anti-idiotype Effects 0.000 description 6
150000001720 carbohydrates Chemical group 0.000 description 6
239000012636 effector Substances 0.000 description 6
239000003623 enhancer Substances 0.000 description 6
230000013595 glycosylation Effects 0.000 description 6
238000006206 glycosylation reaction Methods 0.000 description 6
238000001727 in vivo Methods 0.000 description 6
238000003780 insertion Methods 0.000 description 6
230000037431 insertion Effects 0.000 description 6
230000004807 localization Effects 0.000 description 6
210000004698 lymphocyte Anatomy 0.000 description 6
238000002703 mutagenesis Methods 0.000 description 6
231100000350 mutagenesis Toxicity 0.000 description 6
229910052698 phosphorus Inorganic materials 0.000 description 6
238000012545 processing Methods 0.000 description 6
206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 description 6
238000003127 radioimmunoassay Methods 0.000 description 6
230000028327 secretion Effects 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
230000001225 therapeutic effect Effects 0.000 description 6
229910052721 tungsten Inorganic materials 0.000 description 6
229910052727 yttrium Inorganic materials 0.000 description 6
NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 5
241000894006 Bacteria Species 0.000 description 5
241000282412 Homo Species 0.000 description 5
102000013463 Immunoglobulin Light Chains Human genes 0.000 description 5
108010065825 Immunoglobulin Light Chains Proteins 0.000 description 5
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 5
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 5
108091034117 Oligonucleotide Proteins 0.000 description 5
210000001744 T-lymphocyte Anatomy 0.000 description 5
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 5
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 5
230000021736 acetylation Effects 0.000 description 5
238000006640 acetylation reaction Methods 0.000 description 5
210000003719 b-lymphocyte Anatomy 0.000 description 5
235000020958 biotin Nutrition 0.000 description 5
239000011616 biotin Substances 0.000 description 5
229960002685 biotin Drugs 0.000 description 5
230000030833 cell death Effects 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 5
235000018417 cysteine Nutrition 0.000 description 5
210000003527 eukaryotic cell Anatomy 0.000 description 5
238000003018 immunoassay Methods 0.000 description 5
229940072221 immunoglobulins Drugs 0.000 description 5
230000001965 increasing effect Effects 0.000 description 5
238000013507 mapping Methods 0.000 description 5
230000001537 neural effect Effects 0.000 description 5
COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
102000005962 receptors Human genes 0.000 description 5
108020003175 receptors Proteins 0.000 description 5
238000010561 standard procedure Methods 0.000 description 5
210000001519 tissue Anatomy 0.000 description 5
ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 4
KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 4
241000699802 Cricetulus griseus Species 0.000 description 4
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
108700005091 Immunoglobulin Genes Proteins 0.000 description 4
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 4
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 4
241001529936 Murinae Species 0.000 description 4
241000699660 Mus musculus Species 0.000 description 4
102000047918 Myelin Basic Human genes 0.000 description 4
101710107068 Myelin basic protein Proteins 0.000 description 4
102100026784 Myelin proteolipid protein Human genes 0.000 description 4
241000283973 Oryctolagus cuniculus Species 0.000 description 4
206010035226 Plasma cell myeloma Diseases 0.000 description 4
240000004808 Saccharomyces cerevisiae Species 0.000 description 4
235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 4
PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 4
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 4
239000004473 Threonine Substances 0.000 description 4
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
241000251539 Vertebrata <Metazoa> Species 0.000 description 4
239000002671 adjuvant Substances 0.000 description 4
230000003321 amplification Effects 0.000 description 4
206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 4
230000000890 antigenic effect Effects 0.000 description 4
238000013459 approach Methods 0.000 description 4
230000004071 biological effect Effects 0.000 description 4
210000004899 c-terminal region Anatomy 0.000 description 4
238000004113 cell culture Methods 0.000 description 4
210000004978 chinese hamster ovary cell Anatomy 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
238000010367 cloning Methods 0.000 description 4
230000009260 cross reactivity Effects 0.000 description 4
238000001943 fluorescence-activated cell sorting Methods 0.000 description 4
230000001900 immune effect Effects 0.000 description 4
230000002163 immunogen Effects 0.000 description 4
230000016784 immunoglobulin production Effects 0.000 description 4
230000003993 interaction Effects 0.000 description 4
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 4
229960000310 isoleucine Drugs 0.000 description 4
210000003734 kidney Anatomy 0.000 description 4
229910052751 metal Inorganic materials 0.000 description 4
239000002184 metal Substances 0.000 description 4
201000000050 myeloid neoplasm Diseases 0.000 description 4
230000007935 neutral effect Effects 0.000 description 4
238000003199 nucleic acid amplification method Methods 0.000 description 4
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 4
230000026731 phosphorylation Effects 0.000 description 4
238000006366 phosphorylation reaction Methods 0.000 description 4
230000006798 recombination Effects 0.000 description 4
239000004055 small Interfering RNA Substances 0.000 description 4
208000020431 spinal cord injury Diseases 0.000 description 4
230000004083 survival effect Effects 0.000 description 4
238000012360 testing method Methods 0.000 description 4
238000012546 transfer Methods 0.000 description 4
238000011830 transgenic mouse model Methods 0.000 description 4
-1 tripeptide Proteins 0.000 description 4
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
239000004474 valine Substances 0.000 description 4
230000003612 virological effect Effects 0.000 description 4
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical group OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
102100024643 ATP-binding cassette sub-family D member 1 Human genes 0.000 description 3
201000011452 Adrenoleukodystrophy Diseases 0.000 description 3
208000024827 Alzheimer disease Diseases 0.000 description 3
241000283690 Bos taurus Species 0.000 description 3
241000282693 Cercopithecidae Species 0.000 description 3
108020004705 Codon Proteins 0.000 description 3
241000699800 Cricetinae Species 0.000 description 3
241000196324 Embryophyta Species 0.000 description 3
102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 3
101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 3
208000023105 Huntington disease Diseases 0.000 description 3
102100024102 Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 Human genes 0.000 description 3
108010049137 Member 1 Subfamily D ATP Binding Cassette Transporter Proteins 0.000 description 3
206010028570 Myelopathy Diseases 0.000 description 3
208000012902 Nervous system disease Diseases 0.000 description 3
208000018737 Parkinson disease Diseases 0.000 description 3
241000288906 Primates Species 0.000 description 3
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Chemical group OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
108020004566 Transfer RNA Proteins 0.000 description 3
206010073696 Wallerian degeneration Diseases 0.000 description 3
230000009435 amidation Effects 0.000 description 3
238000007112 amidation reaction Methods 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
230000001588 bifunctional effect Effects 0.000 description 3
230000000903 blocking effect Effects 0.000 description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
230000001413 cellular effect Effects 0.000 description 3
206010008118 cerebral infarction Diseases 0.000 description 3
208000026106 cerebrovascular disease Diseases 0.000 description 3
238000007385 chemical modification Methods 0.000 description 3
238000003776 cleavage reaction Methods 0.000 description 3
230000024203 complement activation Effects 0.000 description 3
230000021615 conjugation Effects 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
125000004122 cyclic group Chemical group 0.000 description 3
230000001086 cytosolic effect Effects 0.000 description 3
231100000599 cytotoxic agent Toxicity 0.000 description 3
210000001671 embryonic stem cell Anatomy 0.000 description 3
230000022244 formylation Effects 0.000 description 3
238000006170 formylation reaction Methods 0.000 description 3
239000000499 gel Substances 0.000 description 3
230000009036 growth inhibition Effects 0.000 description 3
239000001963 growth medium Substances 0.000 description 3
230000036541 health Effects 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
230000028993 immune response Effects 0.000 description 3
230000003902 lesion Effects 0.000 description 3
239000000178 monomer Substances 0.000 description 3
230000016273 neuron death Effects 0.000 description 3
238000011275 oncology therapy Methods 0.000 description 3
210000001672 ovary Anatomy 0.000 description 3
230000036961 partial effect Effects 0.000 description 3
230000008488 polyadenylation Effects 0.000 description 3
230000001323 posttranslational effect Effects 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
230000035755 proliferation Effects 0.000 description 3
230000006337 proteolytic cleavage Effects 0.000 description 3
238000005215 recombination Methods 0.000 description 3
230000010076 replication Effects 0.000 description 3
230000007017 scission Effects 0.000 description 3
238000002741 site-directed mutagenesis Methods 0.000 description 3
239000007787 solid Substances 0.000 description 3
210000000130 stem cell Anatomy 0.000 description 3
230000002194 synthesizing effect Effects 0.000 description 3
239000003053 toxin Substances 0.000 description 3
231100000765 toxin Toxicity 0.000 description 3
108700012359 toxins Proteins 0.000 description 3
241001430294 unidentified retrovirus Species 0.000 description 3
230000008734 wallerian degeneration Effects 0.000 description 3
108010022752 Acetylcholinesterase Proteins 0.000 description 2
102000012440 Acetylcholinesterase Human genes 0.000 description 2
108010085238 Actins Proteins 0.000 description 2
102000007469 Actins Human genes 0.000 description 2
208000011403 Alexander disease Diseases 0.000 description 2
102000002260 Alkaline Phosphatase Human genes 0.000 description 2
108020004774 Alkaline Phosphatase Proteins 0.000 description 2
108090001008 Avidin Proteins 0.000 description 2
102100026189 Beta-galactosidase Human genes 0.000 description 2
241000283707 Capra Species 0.000 description 2
241000701022 Cytomegalovirus Species 0.000 description 2
102000053602 DNA Human genes 0.000 description 2
208000032131 Diabetic Neuropathies Diseases 0.000 description 2
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
206010067601 Dysmyelination Diseases 0.000 description 2
206010058314 Dysplasia Diseases 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
238000012286 ELISA Assay Methods 0.000 description 2
241000283074 Equus asinus Species 0.000 description 2
241000724791 Filamentous phage Species 0.000 description 2
241000287828 Gallus gallus Species 0.000 description 2
208000010055 Globoid Cell Leukodystrophy Diseases 0.000 description 2
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
108010070675 Glutathione transferase Proteins 0.000 description 2
239000004471 Glycine Substances 0.000 description 2
102000003886 Glycoproteins Human genes 0.000 description 2
108090000288 Glycoproteins Proteins 0.000 description 2
102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 2
102100021519 Hemoglobin subunit beta Human genes 0.000 description 2
108091005904 Hemoglobin subunit beta Proteins 0.000 description 2
241000238631 Hexapoda Species 0.000 description 2
108010093488 His-His-His-His-His-His Proteins 0.000 description 2
101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 2
101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 2
108010001336 Horseradish Peroxidase Proteins 0.000 description 2
102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 2
108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 2
102000004195 Isomerases Human genes 0.000 description 2
108090000769 Isomerases Proteins 0.000 description 2
208000028226 Krabbe disease Diseases 0.000 description 2
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-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
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-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
241001467552 Mycobacterium bovis BCG Species 0.000 description 2
108010000123 Myelin-Oligodendrocyte Glycoprotein Proteins 0.000 description 2
102100023302 Myelin-oligodendrocyte glycoprotein Human genes 0.000 description 2
QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical group OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 2
HDFGOPSGAURCEO-UHFFFAOYSA-N N-ethylmaleimide Chemical compound CCN1C(=O)C=CC1=O HDFGOPSGAURCEO-UHFFFAOYSA-N 0.000 description 2
108091093037 Peptide nucleic acid Proteins 0.000 description 2
108010029485 Protein Isoforms Proteins 0.000 description 2
102000001708 Protein Isoforms Human genes 0.000 description 2
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
108091027967 Small hairpin RNA Proteins 0.000 description 2
108020004459 Small interfering RNA Proteins 0.000 description 2
102000003978 Tissue Plasminogen Activator Human genes 0.000 description 2
108090000373 Tissue Plasminogen Activator Proteins 0.000 description 2
241000723873 Tobacco mosaic virus Species 0.000 description 2
102000007238 Transferrin Receptors Human genes 0.000 description 2
208000030886 Traumatic Brain injury Diseases 0.000 description 2
YJQCOFNZVFGCAF-UHFFFAOYSA-N Tunicamycin II Natural products O1C(CC(O)C2C(C(O)C(O2)N2C(NC(=O)C=C2)=O)O)C(O)C(O)C(NC(=O)C=CCCCCCCCCC(C)C)C1OC1OC(CO)C(O)C(O)C1NC(C)=O YJQCOFNZVFGCAF-UHFFFAOYSA-N 0.000 description 2
241000700618 Vaccinia virus Species 0.000 description 2
238000002835 absorbance Methods 0.000 description 2
229940022698 acetylcholinesterase Drugs 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
238000001042 affinity chromatography Methods 0.000 description 2
235000004279 alanine Nutrition 0.000 description 2
230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
235000003704 aspartic acid Nutrition 0.000 description 2
230000003376 axonal effect Effects 0.000 description 2
230000028600 axonogenesis Effects 0.000 description 2
229960000190 bacillus calmette–guérin vaccine Drugs 0.000 description 2
230000001580 bacterial effect Effects 0.000 description 2
239000011324 bead Substances 0.000 description 2
230000008901 benefit Effects 0.000 description 2
108010005774 beta-Galactosidase Proteins 0.000 description 2
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 2
230000008512 biological response Effects 0.000 description 2
230000008499 blood brain barrier function Effects 0.000 description 2
210000001218 blood-brain barrier Anatomy 0.000 description 2
108010006025 bovine growth hormone Proteins 0.000 description 2
235000014633 carbohydrates Nutrition 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
230000008859 change Effects 0.000 description 2
239000003593 chromogenic compound Substances 0.000 description 2
210000000349 chromosome Anatomy 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
150000001875 compounds Chemical class 0.000 description 2
238000004132 cross linking Methods 0.000 description 2
230000009089 cytolysis Effects 0.000 description 2
239000002619 cytotoxin Substances 0.000 description 2
230000003210 demyelinating effect Effects 0.000 description 2
238000004925 denaturation Methods 0.000 description 2
230000036425 denaturation Effects 0.000 description 2
238000001212 derivatisation Methods 0.000 description 2
238000003745 diagnosis Methods 0.000 description 2
239000000032 diagnostic agent Substances 0.000 description 2
229940039227 diagnostic agent Drugs 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
238000012377 drug delivery Methods 0.000 description 2
238000004520 electroporation Methods 0.000 description 2
238000000605 extraction Methods 0.000 description 2
210000002950 fibroblast Anatomy 0.000 description 2
GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
238000002523 gelfiltration Methods 0.000 description 2
230000002068 genetic effect Effects 0.000 description 2
210000004602 germ cell Anatomy 0.000 description 2
235000013922 glutamic acid Nutrition 0.000 description 2
229960002989 glutamic acid Drugs 0.000 description 2
239000004220 glutamic acid Substances 0.000 description 2
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
229910052737 gold Inorganic materials 0.000 description 2
239000010931 gold Substances 0.000 description 2
229960000789 guanidine hydrochloride Drugs 0.000 description 2
PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
238000002744 homologous recombination Methods 0.000 description 2
230000006801 homologous recombination Effects 0.000 description 2
210000004754 hybrid cell Anatomy 0.000 description 2
230000003053 immunization Effects 0.000 description 2
238000002649 immunization Methods 0.000 description 2
230000005847 immunogenicity Effects 0.000 description 2
208000015181 infectious disease Diseases 0.000 description 2
238000005304 joining Methods 0.000 description 2
HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 2
239000002609 medium Substances 0.000 description 2
230000002503 metabolic effect Effects 0.000 description 2
229910021645 metal ion Inorganic materials 0.000 description 2
150000002739 metals Chemical class 0.000 description 2
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
229930182817 methionine Natural products 0.000 description 2
229960000485 methotrexate Drugs 0.000 description 2
230000011987 methylation Effects 0.000 description 2
238000007069 methylation reaction Methods 0.000 description 2
230000003278 mimic effect Effects 0.000 description 2
210000000653 nervous system Anatomy 0.000 description 2
230000006576 neuronal survival Effects 0.000 description 2
239000002245 particle Substances 0.000 description 2
229960003330 pentetic acid Drugs 0.000 description 2
210000001428 peripheral nervous system Anatomy 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
239000002243 precursor Substances 0.000 description 2
210000001236 prokaryotic cell Anatomy 0.000 description 2
230000000069 prophylactic effect Effects 0.000 description 2
230000017854 proteolysis Effects 0.000 description 2
230000002797 proteolythic effect Effects 0.000 description 2
230000002285 radioactive effect Effects 0.000 description 2
239000012857 radioactive material Substances 0.000 description 2
108700020894 rat LINGO1 Proteins 0.000 description 2
238000003259 recombinant expression Methods 0.000 description 2
238000010188 recombinant method Methods 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
238000003757 reverse transcription PCR Methods 0.000 description 2
238000012552 review Methods 0.000 description 2
239000000523 sample Substances 0.000 description 2
230000003248 secreting effect Effects 0.000 description 2
238000004062 sedimentation Methods 0.000 description 2
238000012163 sequencing technique Methods 0.000 description 2
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
239000000243 solution Substances 0.000 description 2
210000000952 spleen Anatomy 0.000 description 2
230000010473 stable expression Effects 0.000 description 2
239000000758 substrate Substances 0.000 description 2
230000001629 suppression Effects 0.000 description 2
125000003396 thiol group Chemical group [H]S* 0.000 description 2
229960000187 tissue plasminogen activator Drugs 0.000 description 2
238000001890 transfection Methods 0.000 description 2
230000009261 transgenic effect Effects 0.000 description 2
230000014616 translation Effects 0.000 description 2
230000014621 translational initiation Effects 0.000 description 2
230000009529 traumatic brain injury Effects 0.000 description 2
ZHSGGJXRNHWHRS-VIDYELAYSA-N tunicamycin Chemical compound O([C@H]1[C@@H]([C@H]([C@@H](O)[C@@H](CC(O)[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C(NC(=O)C=C2)=O)O)O1)O)NC(=O)/C=C/CC(C)C)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)=O ZHSGGJXRNHWHRS-VIDYELAYSA-N 0.000 description 2
MEYZYGMYMLNUHJ-UHFFFAOYSA-N tunicamycin Natural products CC(C)CCCCCCCCCC=CC(=O)NC1C(O)C(O)C(CC(O)C2OC(C(O)C2O)N3C=CC(=O)NC3=O)OC1OC4OC(CO)C(O)C(O)C4NC(=O)C MEYZYGMYMLNUHJ-UHFFFAOYSA-N 0.000 description 2
230000034512 ubiquitination Effects 0.000 description 2
238000010798 ubiquitination Methods 0.000 description 2
241000701161 unidentified adenovirus Species 0.000 description 2
241000701447 unidentified baculovirus Species 0.000 description 2
241001515965 unidentified phage Species 0.000 description 2
230000000007 visual effect Effects 0.000 description 2
238000001262 western blot Methods 0.000 description 2
YMXHPSHLTSZXKH-RVBZMBCESA-N (2,5-dioxopyrrolidin-1-yl) 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoate Chemical compound C([C@H]1[C@H]2NC(=O)N[C@H]2CS1)CCCC(=O)ON1C(=O)CCC1=O YMXHPSHLTSZXKH-RVBZMBCESA-N 0.000 description 1
DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 1
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
101150098072 20 gene Proteins 0.000 description 1
BRMWTNUJHUMWMS-UHFFFAOYSA-N 3-Methylhistidine Natural products CN1C=NC(CC(N)C(O)=O)=C1 BRMWTNUJHUMWMS-UHFFFAOYSA-N 0.000 description 1
HUDPLKWXRLNSPC-UHFFFAOYSA-N 4-aminophthalhydrazide Chemical compound O=C1NNC(=O)C=2C1=CC(N)=CC=2 HUDPLKWXRLNSPC-UHFFFAOYSA-N 0.000 description 1
229940117976 5-hydroxylysine Drugs 0.000 description 1
ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
102100031126 6-phosphogluconolactonase Human genes 0.000 description 1
108010029731 6-phosphogluconolactonase Proteins 0.000 description 1
CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
230000005730 ADP ribosylation Effects 0.000 description 1
206010069754 Acquired gene mutation Diseases 0.000 description 1
102100029457 Adenine phosphoribosyltransferase Human genes 0.000 description 1
108010024223 Adenine phosphoribosyltransferase Proteins 0.000 description 1
108010000239 Aequorin Proteins 0.000 description 1
229920000936 Agarose Polymers 0.000 description 1
102000007698 Alcohol dehydrogenase Human genes 0.000 description 1
108010021809 Alcohol dehydrogenase Proteins 0.000 description 1
244000303258 Annona diversifolia Species 0.000 description 1
235000002198 Annona diversifolia Nutrition 0.000 description 1
206010003445 Ascites Diseases 0.000 description 1
108010024976 Asparaginase Proteins 0.000 description 1
102000015790 Asparaginase Human genes 0.000 description 1
208000001827 Ataxia with vitamin E deficiency Diseases 0.000 description 1
241000271566 Aves Species 0.000 description 1
102100038080 B-cell receptor CD22 Human genes 0.000 description 1
244000063299 Bacillus subtilis Species 0.000 description 1
235000014469 Bacillus subtilis Nutrition 0.000 description 1
208000006373 Bell palsy Diseases 0.000 description 1
241000701822 Bovine papillomavirus Species 0.000 description 1
102100032912 CD44 antigen Human genes 0.000 description 1
108010021064 CTLA-4 Antigen Proteins 0.000 description 1
229940045513 CTLA4 antagonist Drugs 0.000 description 1
101100244725 Caenorhabditis elegans pef-1 gene Proteins 0.000 description 1
241000282836 Camelus dromedarius Species 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
102100035882 Catalase Human genes 0.000 description 1
108010053835 Catalase Proteins 0.000 description 1
241000701489 Cauliflower mosaic virus Species 0.000 description 1
241000700198 Cavia Species 0.000 description 1
241000700199 Cavia porcellus Species 0.000 description 1
241000251730 Chondrichthyes Species 0.000 description 1
108700010070 Codon Usage Proteins 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
241000186216 Corynebacterium Species 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
101710112752 Cytotoxin Proteins 0.000 description 1
IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
GUBGYTABKSRVRQ-WFVLMXAXSA-N DEAE-cellulose Chemical compound OC1C(O)C(O)C(CO)O[C@H]1O[C@@H]1C(CO)OC(O)C(O)C1O GUBGYTABKSRVRQ-WFVLMXAXSA-N 0.000 description 1
101150074155 DHFR gene Proteins 0.000 description 1
102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
XPDXVDYUQZHFPV-UHFFFAOYSA-N Dansyl Chloride Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(Cl)(=O)=O XPDXVDYUQZHFPV-UHFFFAOYSA-N 0.000 description 1
CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
102100024746 Dihydrofolate reductase Human genes 0.000 description 1
108010016626 Dipeptides Proteins 0.000 description 1
206010061818 Disease progression Diseases 0.000 description 1
241000588921 Enterobacteriaceae Species 0.000 description 1
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 1
241000283086 Equidae Species 0.000 description 1
241000283073 Equus caballus Species 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
108700039691 Genetic Promoter Regions Proteins 0.000 description 1
108010073178 Glucan 1,4-alpha-Glucosidase Proteins 0.000 description 1
102100022624 Glucoamylase Human genes 0.000 description 1
239000004366 Glucose oxidase Substances 0.000 description 1
108010015776 Glucose oxidase Proteins 0.000 description 1
108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 1
241000606768 Haemophilus influenzae Species 0.000 description 1
102000002812 Heat-Shock Proteins Human genes 0.000 description 1
108010004889 Heat-Shock Proteins Proteins 0.000 description 1
101710154606 Hemagglutinin Proteins 0.000 description 1
101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 1
101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
101000852815 Homo sapiens Insulin receptor Proteins 0.000 description 1
101100128251 Homo sapiens LINGO1 gene Proteins 0.000 description 1
101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 1
101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 1
101000766306 Homo sapiens Serotransferrin Proteins 0.000 description 1
101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
241000701024 Human betaherpesvirus 5 Species 0.000 description 1
101100321817 Human parvovirus B19 (strain HV) 7.5K gene Proteins 0.000 description 1
PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical group O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 1
102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 description 1
102000009438 IgE Receptors Human genes 0.000 description 1
108010073816 IgE Receptors Proteins 0.000 description 1
229930010555 Inosine Natural products 0.000 description 1
UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
102100034343 Integrase Human genes 0.000 description 1
102000003996 Interferon-beta Human genes 0.000 description 1
108090000467 Interferon-beta Proteins 0.000 description 1
102000014150 Interferons Human genes 0.000 description 1
108010050904 Interferons Proteins 0.000 description 1
102000015696 Interleukins Human genes 0.000 description 1
108010063738 Interleukins Proteins 0.000 description 1
108091092195 Intron Proteins 0.000 description 1
108010025815 Kanamycin Kinase Proteins 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
108010092694 L-Selectin Proteins 0.000 description 1
UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
102100033467 L-selectin Human genes 0.000 description 1
102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 1
108060001084 Luciferase Proteins 0.000 description 1
239000005089 Luciferase Substances 0.000 description 1
DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
102000013460 Malate Dehydrogenase Human genes 0.000 description 1
108010026217 Malate Dehydrogenase Proteins 0.000 description 1
102000018697 Membrane Proteins Human genes 0.000 description 1
108010052285 Membrane Proteins Proteins 0.000 description 1
201000011442 Metachromatic leukodystrophy Diseases 0.000 description 1
102000003792 Metallothionein Human genes 0.000 description 1
108090000157 Metallothionein Proteins 0.000 description 1
108010059724 Micrococcal Nuclease Proteins 0.000 description 1
241000713333 Mouse mammary tumor virus Species 0.000 description 1
101000933447 Mus musculus Beta-glucuronidase Proteins 0.000 description 1
JDHILDINMRGULE-LURJTMIESA-N N(pros)-methyl-L-histidine Chemical group CN1C=NC=C1C[C@H](N)C(O)=O JDHILDINMRGULE-LURJTMIESA-N 0.000 description 1
GHAZCVNUKKZTLG-UHFFFAOYSA-N N-ethyl-succinimide Natural products CCN1C(=O)CCC1=O GHAZCVNUKKZTLG-UHFFFAOYSA-N 0.000 description 1
108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
208000028389 Nerve injury Diseases 0.000 description 1
208000001738 Nervous System Trauma Diseases 0.000 description 1
238000000636 Northern blotting Methods 0.000 description 1
108010005298 Oligodendrocyte-Myelin Glycoprotein Proteins 0.000 description 1
102100026746 Oligodendrocyte-myelin glycoprotein Human genes 0.000 description 1
108020005187 Oligonucleotide Probes Proteins 0.000 description 1
108010038807 Oligopeptides Proteins 0.000 description 1
102000015636 Oligopeptides Human genes 0.000 description 1
208000003435 Optic Neuritis Diseases 0.000 description 1
208000030768 Optic nerve injury Diseases 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
101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
108090000526 Papain Proteins 0.000 description 1
206010033799 Paralysis Diseases 0.000 description 1
102000057297 Pepsin A Human genes 0.000 description 1
108090000284 Pepsin A Proteins 0.000 description 1
108010004729 Phycoerythrin Proteins 0.000 description 1
241000235648 Pichia Species 0.000 description 1
241000709664 Picornaviridae Species 0.000 description 1
241000276498 Pollachius virens Species 0.000 description 1
241001505332 Polyomavirus sp. Species 0.000 description 1
239000004365 Protease Substances 0.000 description 1
101710176177 Protein A56 Proteins 0.000 description 1
108010001267 Protein Subunits Proteins 0.000 description 1
102000002067 Protein Subunits Human genes 0.000 description 1
ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 1
108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
102000006382 Ribonucleases Human genes 0.000 description 1
108010083644 Ribonucleases Proteins 0.000 description 1
238000011579 SCID mouse model Methods 0.000 description 1
241000235070 Saccharomyces Species 0.000 description 1
241000607142 Salmonella Species 0.000 description 1
206010039491 Sarcoma Diseases 0.000 description 1
241000700584 Simplexvirus Species 0.000 description 1
108020004682 Single-Stranded DNA Proteins 0.000 description 1
108091081024 Start codon Proteins 0.000 description 1
108010090804 Streptavidin Proteins 0.000 description 1
241000194017 Streptococcus Species 0.000 description 1
108091008874 T cell receptors Proteins 0.000 description 1
102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
108010022394 Threonine synthase Proteins 0.000 description 1
102000006601 Thymidine Kinase Human genes 0.000 description 1
108020004440 Thymidine kinase Proteins 0.000 description 1
108010033576 Transferrin Receptors Proteins 0.000 description 1
108700019146 Transgenes Proteins 0.000 description 1
108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
108010046334 Urease Proteins 0.000 description 1
208000036826 VIIth nerve paralysis Diseases 0.000 description 1
206010047631 Vitamin E deficiency Diseases 0.000 description 1
ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical class C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 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
238000011374 additional therapy Methods 0.000 description 1
230000002411 adverse Effects 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
230000004075 alteration Effects 0.000 description 1
WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
230000006229 amino acid addition Effects 0.000 description 1
150000003862 amino acid derivatives Chemical class 0.000 description 1
229940126575 aminoglycoside Drugs 0.000 description 1
238000013103 analytical ultracentrifugation Methods 0.000 description 1
238000010171 animal model Methods 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
238000000137 annealing Methods 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000000340 anti-metabolite Effects 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
238000009175 antibody therapy Methods 0.000 description 1
210000000628 antibody-producing cell Anatomy 0.000 description 1
229940100197 antimetabolite Drugs 0.000 description 1
239000002256 antimetabolite Substances 0.000 description 1
230000010516 arginylation Effects 0.000 description 1
229960003272 asparaginase Drugs 0.000 description 1
DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 1
125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
230000001363 autoimmune Effects 0.000 description 1
238000000376 autoradiography Methods 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
238000013357 binding ELISA Methods 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
238000010256 biochemical assay Methods 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
239000003139 biocide Substances 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
238000001815 biotherapy Methods 0.000 description 1
210000002459 blastocyst Anatomy 0.000 description 1
238000006664 bond formation reaction Methods 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
239000012830 cancer therapeutic Substances 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
230000024245 cell differentiation Effects 0.000 description 1
230000003915 cell function Effects 0.000 description 1
230000007910 cell fusion Effects 0.000 description 1
230000011748 cell maturation Effects 0.000 description 1
230000007248 cellular mechanism Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
239000000919 ceramic Substances 0.000 description 1
208000019065 cervical carcinoma Diseases 0.000 description 1
238000002144 chemical decomposition reaction Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
238000011210 chromatographic step Methods 0.000 description 1
238000004737 colorimetric analysis Methods 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
230000006957 competitive inhibition Effects 0.000 description 1
230000004154 complement system Effects 0.000 description 1
230000001268 conjugating effect Effects 0.000 description 1
238000010276 construction Methods 0.000 description 1
239000000599 controlled substance Substances 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
239000003246 corticosteroid Substances 0.000 description 1
229960001334 corticosteroids Drugs 0.000 description 1
239000007822 coupling agent Substances 0.000 description 1
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
229940127089 cytotoxic agent Drugs 0.000 description 1
239000002254 cytotoxic agent Substances 0.000 description 1
230000001472 cytotoxic effect Effects 0.000 description 1
YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
230000017858 demethylation Effects 0.000 description 1
238000010520 demethylation reaction Methods 0.000 description 1
210000001787 dendrite Anatomy 0.000 description 1
238000013461 design Methods 0.000 description 1
238000000502 dialysis Methods 0.000 description 1
108020001096 dihydrofolate reductase Proteins 0.000 description 1
238000011979 disease modifying therapy Methods 0.000 description 1
230000005750 disease progression Effects 0.000 description 1
238000009826 distribution Methods 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
230000005684 electric field Effects 0.000 description 1
238000001962 electrophoresis Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
238000000295 emission spectrum Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
230000002124 endocrine Effects 0.000 description 1
210000002889 endothelial cell Anatomy 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
238000006911 enzymatic reaction Methods 0.000 description 1
238000001976 enzyme digestion Methods 0.000 description 1
108010002591 epsilon receptor Proteins 0.000 description 1
YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical group NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
239000003797 essential amino acid Substances 0.000 description 1
235000020776 essential amino acid Nutrition 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
239000000284 extract Substances 0.000 description 1
201000003264 familial isolated deficiency of vitamin E Diseases 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
239000012530 fluid Substances 0.000 description 1
238000001506 fluorescence spectroscopy Methods 0.000 description 1
230000005714 functional activity Effects 0.000 description 1
230000006251 gamma-carboxylation Effects 0.000 description 1
238000001502 gel electrophoresis Methods 0.000 description 1
238000003500 gene array Methods 0.000 description 1
238000003197 gene knockdown Methods 0.000 description 1
229940116332 glucose oxidase Drugs 0.000 description 1
235000019420 glucose oxidase Nutrition 0.000 description 1
108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
ZJYYHGLJYGJLLN-UHFFFAOYSA-N guanidinium thiocyanate Chemical compound SC#N.NC(N)=N ZJYYHGLJYGJLLN-UHFFFAOYSA-N 0.000 description 1
150000003278 haem Chemical group 0.000 description 1
229910001385 heavy metal Inorganic materials 0.000 description 1
230000002949 hemolytic effect Effects 0.000 description 1
239000012510 hollow fiber Substances 0.000 description 1
239000013029 homogenous suspension Substances 0.000 description 1
102000047882 human INSR Human genes 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
238000012872 hydroxylapatite chromatography Methods 0.000 description 1
230000033444 hydroxylation Effects 0.000 description 1
238000005805 hydroxylation reaction Methods 0.000 description 1
229960002591 hydroxyproline Drugs 0.000 description 1
230000009610 hypersensitivity Effects 0.000 description 1
238000003384 imaging method Methods 0.000 description 1
229940127121 immunoconjugate Drugs 0.000 description 1
238000011532 immunohistochemical staining Methods 0.000 description 1
238000003364 immunohistochemistry Methods 0.000 description 1
238000001114 immunoprecipitation Methods 0.000 description 1
238000012744 immunostaining Methods 0.000 description 1
229960001438 immunostimulant agent Drugs 0.000 description 1
239000003022 immunostimulating agent Substances 0.000 description 1
230000003308 immunostimulating effect Effects 0.000 description 1
239000002596 immunotoxin Substances 0.000 description 1
238000000099 in vitro assay Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
210000003000 inclusion body Anatomy 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
230000028709 inflammatory response Effects 0.000 description 1
206010022000 influenza Diseases 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
229960003786 inosine Drugs 0.000 description 1
230000010354 integration Effects 0.000 description 1
230000002452 interceptive effect Effects 0.000 description 1
229960001388 interferon-beta Drugs 0.000 description 1
229940047124 interferons Drugs 0.000 description 1
229940047122 interleukins Drugs 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
229940065638 intron a Drugs 0.000 description 1
230000026045 iodination Effects 0.000 description 1
238000006192 iodination reaction Methods 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
150000002540 isothiocyanates Chemical class 0.000 description 1
108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
238000011813 knockout mouse model Methods 0.000 description 1
238000002372 labelling Methods 0.000 description 1
101150066555 lacZ gene Proteins 0.000 description 1
229910052747 lanthanoid Inorganic materials 0.000 description 1
150000002602 lanthanoids Chemical class 0.000 description 1
210000004901 leucine-rich repeat Anatomy 0.000 description 1
230000033001 locomotion Effects 0.000 description 1
238000004020 luminiscence type Methods 0.000 description 1
210000001165 lymph node Anatomy 0.000 description 1
210000003563 lymphoid tissue Anatomy 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
238000000968 medical method and process Methods 0.000 description 1
HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
239000011325 microbead Substances 0.000 description 1
230000002906 microbiologic effect Effects 0.000 description 1
244000005700 microbiome Species 0.000 description 1
239000003094 microcapsule Substances 0.000 description 1
238000000520 microinjection Methods 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
230000037230 mobility Effects 0.000 description 1
239000003607 modifier Substances 0.000 description 1
238000010369 molecular cloning Methods 0.000 description 1
102000051367 mu Opioid Receptors Human genes 0.000 description 1
HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
229960000951 mycophenolic acid Drugs 0.000 description 1
230000007498 myristoylation Effects 0.000 description 1
ZTLGJPIZUOVDMT-UHFFFAOYSA-N n,n-dichlorotriazin-4-amine Chemical compound ClN(Cl)C1=CC=NN=N1 ZTLGJPIZUOVDMT-UHFFFAOYSA-N 0.000 description 1
230000032405 negative regulation of neuron apoptotic process Effects 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
230000005709 nerve cell growth Effects 0.000 description 1
230000008764 nerve damage Effects 0.000 description 1
210000002241 neurite Anatomy 0.000 description 1
210000004498 neuroglial cell Anatomy 0.000 description 1
230000004031 neuronal differentiation Effects 0.000 description 1
230000007511 neuronal proliferation Effects 0.000 description 1
201000001119 neuropathy Diseases 0.000 description 1
230000007823 neuropathy Effects 0.000 description 1
239000002858 neurotransmitter agent Substances 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
239000002751 oligonucleotide probe Substances 0.000 description 1
150000002482 oligosaccharides Polymers 0.000 description 1
230000014207 opsonization Effects 0.000 description 1
229960003104 ornithine Drugs 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
229940055729 papain Drugs 0.000 description 1
235000019834 papain Nutrition 0.000 description 1
230000005298 paramagnetic effect Effects 0.000 description 1
244000052769 pathogen Species 0.000 description 1
230000006320 pegylation Effects 0.000 description 1
229940111202 pepsin Drugs 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
210000005259 peripheral blood Anatomy 0.000 description 1
239000011886 peripheral blood Substances 0.000 description 1
210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
208000033808 peripheral neuropathy Diseases 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
RXNXLAHQOVLMIE-UHFFFAOYSA-N phenyl 10-methylacridin-10-ium-9-carboxylate Chemical compound C12=CC=CC=C2[N+](C)=C2C=CC=CC2=C1C(=O)OC1=CC=CC=C1 RXNXLAHQOVLMIE-UHFFFAOYSA-N 0.000 description 1
DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 1
230000003169 placental effect Effects 0.000 description 1
229920001983 poloxamer Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229920005862 polyol Polymers 0.000 description 1
150000003077 polyols Chemical class 0.000 description 1
239000013641 positive control Substances 0.000 description 1
238000002600 positron emission tomography Methods 0.000 description 1
230000004481 post-translational protein modification Effects 0.000 description 1
230000001124 posttranscriptional effect Effects 0.000 description 1
230000013823 prenylation Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
238000004393 prognosis Methods 0.000 description 1
230000012846 protein folding Effects 0.000 description 1
230000009145 protein modification Effects 0.000 description 1
238000001243 protein synthesis Methods 0.000 description 1
230000004850 protein–protein interaction Effects 0.000 description 1
XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 1
210000001938 protoplast Anatomy 0.000 description 1
230000006340 racemization Effects 0.000 description 1
238000000163 radioactive labelling Methods 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000001172 regenerating effect Effects 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
230000003252 repetitive effect Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
238000002702 ribosome display Methods 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
210000003935 rough endoplasmic reticulum Anatomy 0.000 description 1
238000003118 sandwich ELISA Methods 0.000 description 1
238000013341 scale-up Methods 0.000 description 1
210000004116 schwann cell Anatomy 0.000 description 1
239000006152 selective media Substances 0.000 description 1
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
238000001542 size-exclusion chromatography Methods 0.000 description 1
AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
230000037439 somatic mutation Effects 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
125000006850 spacer group Chemical group 0.000 description 1
210000003594 spinal ganglia Anatomy 0.000 description 1
210000004988 splenocyte Anatomy 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
230000019635 sulfation Effects 0.000 description 1
238000005670 sulfation reaction Methods 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
239000013589 supplement Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000004114 suspension culture Methods 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
230000000946 synaptic effect Effects 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
238000012549 training Methods 0.000 description 1
230000005030 transcription termination Effects 0.000 description 1
108091008023 transcriptional regulators Proteins 0.000 description 1
230000010474 transient expression Effects 0.000 description 1
238000013519 translation Methods 0.000 description 1
230000001296 transplacental effect Effects 0.000 description 1
208000009174 transverse myelitis Diseases 0.000 description 1
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 1
206010044652 trigeminal neuralgia Diseases 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
229940079023 tysabri Drugs 0.000 description 1
ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
HFTAFOQKODTIJY-UHFFFAOYSA-N umbelliferone Natural products Cc1cc2C=CC(=O)Oc2cc1OCC=CC(C)(C)O HFTAFOQKODTIJY-UHFFFAOYSA-N 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
108020001612 μ-opioid receptors Proteins 0.000 description 1

JP2014103293A 2008-07-09 2014-05-19 Ｌｉｎｇｏ抗体または断片を含む組成物 Withdrawn JP2014144017A (ja)