CA2490644A1 - Phosphorothioates d'oligonucleotide hybrides - Google Patents
Phosphorothioates d'oligonucleotide hybrides Download PDFInfo
- Publication number
- CA2490644A1 CA2490644A1 CA002490644A CA2490644A CA2490644A1 CA 2490644 A1 CA2490644 A1 CA 2490644A1 CA 002490644 A CA002490644 A CA 002490644A CA 2490644 A CA2490644 A CA 2490644A CA 2490644 A1 CA2490644 A1 CA 2490644A1
- Authority
- CA
- Canada
- Prior art keywords
- oligonucleotide
- oligonucleotides
- virus
- phosphorothioate
- phosphorodithioate
- 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.)
- Abandoned
Links
- 108091034117 Oligonucleotide Proteins 0.000 title claims abstract description 179
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 title description 18
- 239000002342 ribonucleoside Substances 0.000 claims abstract description 25
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims abstract description 20
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 claims abstract description 15
- 239000005549 deoxyribonucleoside Substances 0.000 claims abstract description 14
- 150000007523 nucleic acids Chemical group 0.000 claims description 33
- 241000700605 Viruses Species 0.000 claims description 29
- 108090000623 proteins and genes Proteins 0.000 claims description 28
- 230000000295 complement effect Effects 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 22
- 244000052769 pathogen Species 0.000 claims description 20
- 230000014509 gene expression Effects 0.000 claims description 19
- 230000001413 cellular effect Effects 0.000 claims description 18
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 13
- 230000001225 therapeutic effect Effects 0.000 claims description 11
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 claims description 8
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 4
- 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 abstract description 82
- 102100034343 Integrase Human genes 0.000 abstract description 22
- 101710203526 Integrase Proteins 0.000 abstract description 22
- 230000004913 activation Effects 0.000 abstract description 11
- 101710163270 Nuclease Proteins 0.000 abstract description 9
- 230000015572 biosynthetic process Effects 0.000 abstract description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 17
- 108091028664 Ribonucleotide Proteins 0.000 description 17
- 239000002336 ribonucleotide Substances 0.000 description 17
- 239000000074 antisense oligonucleotide Substances 0.000 description 15
- 238000012230 antisense oligonucleotides Methods 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 125000002652 ribonucleotide group Chemical group 0.000 description 14
- 108020004707 nucleic acids Proteins 0.000 description 12
- 102000039446 nucleic acids Human genes 0.000 description 12
- 201000010099 disease Diseases 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 8
- 239000002777 nucleoside Substances 0.000 description 8
- 229940124276 oligodeoxyribonucleotide Drugs 0.000 description 8
- 150000004713 phosphodiesters Chemical class 0.000 description 8
- 230000001629 suppression Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol group Chemical group [C@@H]1(CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)[C@H](C)CCCC(C)C HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 125000003835 nucleoside group Chemical group 0.000 description 5
- 239000002773 nucleotide Substances 0.000 description 5
- 125000003729 nucleotide group Chemical group 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- 241000725303 Human immunodeficiency virus Species 0.000 description 4
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 4
- 241000714474 Rous sarcoma virus Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000005547 deoxyribonucleotide Substances 0.000 description 4
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 4
- 125000001475 halogen functional group Chemical group 0.000 description 4
- 238000009396 hybridization Methods 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108091027075 5S-rRNA precursor Proteins 0.000 description 3
- 241000701806 Human papillomavirus Species 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical class OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 230000001293 nucleolytic effect Effects 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 150000008298 phosphoramidates Chemical class 0.000 description 3
- 230000004962 physiological condition Effects 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 108010062513 snake venom phosphodiesterase I Proteins 0.000 description 3
- -1 vitro Chemical group 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- 241000711975 Vesicular stomatitis virus Species 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229940124558 contraceptive agent Drugs 0.000 description 2
- 239000003433 contraceptive agent Substances 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 230000001036 exonucleolytic effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 201000004792 malaria Diseases 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 241000712461 unidentified influenza virus Species 0.000 description 2
- 244000052613 viral pathogen Species 0.000 description 2
- 210000002845 virion Anatomy 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-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
- 102000002226 Alkyl and Aryl Transferases Human genes 0.000 description 1
- 108010014722 Alkyl and Aryl Transferases Proteins 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000004881 Amebiasis Diseases 0.000 description 1
- 206010001980 Amoebiasis Diseases 0.000 description 1
- 102000015427 Angiotensins Human genes 0.000 description 1
- 108010064733 Angiotensins Proteins 0.000 description 1
- 201000002909 Aspergillosis Diseases 0.000 description 1
- 208000036641 Aspergillus infections Diseases 0.000 description 1
- 206010005098 Blastomycosis Diseases 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 206010007134 Candida infections Diseases 0.000 description 1
- 102000006378 Catechol O-methyltransferase Human genes 0.000 description 1
- 108020002739 Catechol O-methyltransferase Proteins 0.000 description 1
- 208000026368 Cestode infections Diseases 0.000 description 1
- 208000022636 Cestode infectious disease Diseases 0.000 description 1
- 201000006082 Chickenpox Diseases 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 206010008803 Chromoblastomycosis Diseases 0.000 description 1
- 208000015116 Chromomycosis Diseases 0.000 description 1
- 241000223205 Coccidioides immitis Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 108020004394 Complementary RNA Proteins 0.000 description 1
- 208000008953 Cryptosporidiosis Diseases 0.000 description 1
- 206010011502 Cryptosporidiosis infection Diseases 0.000 description 1
- 240000008067 Cucumis sativus Species 0.000 description 1
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 1
- 206010012504 Dermatophytosis Diseases 0.000 description 1
- 102000013444 Diacylglycerol Cholinephosphotransferase Human genes 0.000 description 1
- 108010051225 Diacylglycerol cholinephosphotransferase Proteins 0.000 description 1
- 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 1
- 238000002965 ELISA Methods 0.000 description 1
- 206010014523 Embolism and thrombosis Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- 101150096243 FENS gene Proteins 0.000 description 1
- 201000006353 Filariasis Diseases 0.000 description 1
- 208000007212 Foot-and-Mouth Disease Diseases 0.000 description 1
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 241001147447 Heliothis zea nudivirus Species 0.000 description 1
- 208000015336 Helminthic disease Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 241000094682 Hetaerina duplex Species 0.000 description 1
- 201000002563 Histoplasmosis Diseases 0.000 description 1
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010021024 Hypolipidaemia Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 241001460074 Microsporum distortum Species 0.000 description 1
- 102000010909 Monoamine Oxidase Human genes 0.000 description 1
- 108010062431 Monoamine oxidase Proteins 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 101710167853 N-methyltransferase Proteins 0.000 description 1
- 229910017974 NH40H Inorganic materials 0.000 description 1
- 241000244206 Nematoda Species 0.000 description 1
- 208000000291 Nematode infections Diseases 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 1
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 208000005384 Pneumocystis Pneumonia Diseases 0.000 description 1
- 206010073755 Pneumocystis jirovecii pneumonia Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 108090001066 Racemases and epimerases Proteins 0.000 description 1
- 102100028255 Renin Human genes 0.000 description 1
- 108090000783 Renin Proteins 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 208000034712 Rickettsia Infections Diseases 0.000 description 1
- 206010039207 Rocky Mountain Spotted Fever Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 208000019802 Sexually transmitted disease Diseases 0.000 description 1
- 206010041736 Sporotrichosis Diseases 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 208000002474 Tinea Diseases 0.000 description 1
- 201000005485 Toxoplasmosis Diseases 0.000 description 1
- 206010044608 Trichiniasis Diseases 0.000 description 1
- 208000005448 Trichomonas Infections Diseases 0.000 description 1
- 206010044620 Trichomoniasis Diseases 0.000 description 1
- 241000038912 Uloma Species 0.000 description 1
- 206010046980 Varicella Diseases 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 208000000260 Warts Diseases 0.000 description 1
- 208000003152 Yellow Fever Diseases 0.000 description 1
- 241000710772 Yellow fever virus Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 201000009361 ascariasis Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 201000003984 candidiasis Diseases 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 201000003486 coccidioidomycosis Diseases 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002616 endonucleolytic effect Effects 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 201000006592 giardiasis Diseases 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000016087 ovulation Effects 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 208000003154 papilloma Diseases 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- 201000000317 pneumocystosis Diseases 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 108010066481 ribonuclease F Proteins 0.000 description 1
- 201000004409 schistosomiasis Diseases 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 201000010153 skin papilloma Diseases 0.000 description 1
- 230000019100 sperm motility Effects 0.000 description 1
- 230000021595 spermatogenesis Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 208000003982 trichinellosis Diseases 0.000 description 1
- 201000007588 trichinosis Diseases 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000006648 viral gene expression Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/918,239 US5652355A (en) | 1992-07-23 | 1992-07-23 | Hybrid oligonucleotide phosphorothioates |
US07/918,239 | 1992-07-23 | ||
CA002140649A CA2140649C (fr) | 1992-07-23 | 1993-07-22 | Phosphorothioates d'oligonucleotide hybrides |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002140649A Division CA2140649C (fr) | 1992-07-23 | 1993-07-22 | Phosphorothioates d'oligonucleotide hybrides |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2490644A1 true CA2490644A1 (fr) | 1994-02-03 |
Family
ID=34275878
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002490644A Abandoned CA2490644A1 (fr) | 1992-07-23 | 1993-07-22 | Phosphorothioates d'oligonucleotide hybrides |
Country Status (1)
Country | Link |
---|---|
CA (1) | CA2490644A1 (fr) |
-
1993
- 1993-07-22 CA CA002490644A patent/CA2490644A1/fr not_active Abandoned
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0650493B1 (fr) | Phosphorothioates d'oligonucleotides hybrides | |
US6143881A (en) | Hybrid oligonucleotide phosphorothioates | |
US6346614B1 (en) | Hybrid oligonucleotide phosphorothioates | |
WO1994002498A9 (fr) | Phosphorothioates d'oligonucleotides hybrides | |
EP0649467B1 (fr) | Oligonucleotides auto-stabilises utiles comme agents therapeutiques | |
EP0677056B1 (fr) | Alkylphosphonates et alkylphosphonothioates d'oligonucleotides | |
US5929226A (en) | Antisense oligonucleotide alkylphosphonothioates and arylphospohonothioates | |
Cohen | Antisense oligodeoxynucleotides as antiviral agents | |
Tang et al. | Self-stabilized antisense oligodeoxynucleotide phosphorothioates: properties and anti-HIV activity | |
US6015886A (en) | Oligonucleotide phosphate esters | |
US5684147A (en) | Therapeutic anti-HIV anti-viral oligonucleotides and pharmaceutical formulations thereof | |
JP2001501614A (ja) | 三つの構成成分からなるキメラアンチセンスオリゴヌクレオチド | |
CA2490644A1 (fr) | Phosphorothioates d'oligonucleotide hybrides |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
FZDE | Dead |