JP2003526628A5 - - Google Patents

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Publication number

JP2003526628A5

JP2003526628A5 JP2001517689A JP2001517689A JP2003526628A5 JP 2003526628 A5 JP2003526628 A5 JP 2003526628A5 JP 2001517689 A JP2001517689 A JP 2001517689A JP 2001517689 A JP2001517689 A JP 2001517689A JP 2003526628 A5 JP2003526628 A5 JP 2003526628A5

Authority

JP

Japan

Prior art keywords

nucleoside

cpg dinucleotide

cpg

oligonucleotide

dinucleotide

Prior art date

2000-08-14

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.)

Granted

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• 239000002777 nucleoside Substances 0.000 description 113
• 150000003833 nucleoside derivatives Chemical class 0.000 description 106
• 108091029430 CpG site Proteins 0.000 description 100
• 108091034117 Oligonucleotide Proteins 0.000 description 48
• 239000000074 antisense oligonucleotide Substances 0.000 description 13
• 238000012230 antisense oligonucleotides Methods 0.000 description 13
• 230000003308 immunostimulating effect Effects 0.000 description 13
• 238000000034 method Methods 0.000 description 12
• 230000000295 complement effect Effects 0.000 description 10
• 241000713772 Human immunodeficiency virus 1 Species 0.000 description 9
• 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 9
• 108700004026 gag Genes Proteins 0.000 description 9
• 101150098622 gag gene Proteins 0.000 description 8
• 108700004030 rev Genes Proteins 0.000 description 8
• 125000003835 nucleoside group Chemical group 0.000 description 7
• 101150098213 rev gene Proteins 0.000 description 7
• 102100029974 GTPase HRas Human genes 0.000 description 5
• 101000584633 Homo sapiens GTPase HRas Proteins 0.000 description 5
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 5
• 241000124008 Mammalia Species 0.000 description 4
• 230000000692 anti-sense effect Effects 0.000 description 4
• 230000000694 effects Effects 0.000 description 4
• 238000006243 chemical reaction Methods 0.000 description 2
• 230000028993 immune response Effects 0.000 description 2
• 239000002773 nucleotide Substances 0.000 description 2
• 125000003729 nucleotide group Chemical group 0.000 description 2
• 102000016914 ras Proteins Human genes 0.000 description 2
• 108010014186 ras Proteins Proteins 0.000 description 2
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
• 241000701022 Cytomegalovirus Species 0.000 description 1
• 108700020121 Human Immunodeficiency Virus-1 rev Proteins 0.000 description 1
• 206010038910 Retinitis Diseases 0.000 description 1
• RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
• 238000001516 cell proliferation assay Methods 0.000 description 1
• 238000007385 chemical modification Methods 0.000 description 1
• 201000010099 disease Diseases 0.000 description 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
• 239000003814 drug Substances 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 239000000178 monomer Substances 0.000 description 1
• 108020004707 nucleic acids Proteins 0.000 description 1
• 150000007523 nucleic acids Chemical class 0.000 description 1
• 102000039446 nucleic acids Human genes 0.000 description 1
• 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
• 150000008300 phosphoramidites Chemical class 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 239000002342 ribonucleoside Substances 0.000 description 1
• 210000004989 spleen cell Anatomy 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1