CA2521127C - Polymerase inhibitor and method of using same - Google Patents
Polymerase inhibitor and method of using same Download PDFInfo
- Publication number
- CA2521127C CA2521127C CA2521127A CA2521127A CA2521127C CA 2521127 C CA2521127 C CA 2521127C CA 2521127 A CA2521127 A CA 2521127A CA 2521127 A CA2521127 A CA 2521127A CA 2521127 C CA2521127 C CA 2521127C
- Authority
- CA
- Canada
- Prior art keywords
- nucleic acid
- polymerase
- polymerase inhibitor
- acid sequence
- inhibitor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 229940123066 Polymerase inhibitor Drugs 0.000 title claims abstract description 92
- 238000000034 method Methods 0.000 title claims abstract description 79
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 226
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 182
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 182
- 238000006243 chemical reaction Methods 0.000 claims abstract description 56
- 230000003321 amplification Effects 0.000 claims abstract description 55
- 238000003199 nucleic acid amplification method Methods 0.000 claims abstract description 55
- 102000004190 Enzymes Human genes 0.000 claims abstract description 29
- 108090000790 Enzymes Proteins 0.000 claims abstract description 29
- 239000003112 inhibitor Substances 0.000 claims abstract description 27
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 32
- 108020004414 DNA Proteins 0.000 claims description 22
- 239000011541 reaction mixture Substances 0.000 claims description 20
- 238000002844 melting Methods 0.000 claims description 16
- 230000008018 melting Effects 0.000 claims description 16
- 239000002773 nucleotide Substances 0.000 claims description 11
- 125000003729 nucleotide group Chemical group 0.000 claims description 11
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 238000000137 annealing Methods 0.000 claims description 6
- 230000000903 blocking effect Effects 0.000 claims description 6
- 108060002716 Exonuclease Proteins 0.000 claims description 4
- 230000015556 catabolic process Effects 0.000 claims description 4
- 238000006731 degradation reaction Methods 0.000 claims description 4
- 102000013165 exonuclease Human genes 0.000 claims description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 45
- 238000003752 polymerase chain reaction Methods 0.000 description 30
- 239000013615 primer Substances 0.000 description 28
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 19
- 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 19
- 102100034343 Integrase Human genes 0.000 description 18
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 14
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 13
- 229910052739 hydrogen Inorganic materials 0.000 description 13
- 239000001257 hydrogen Substances 0.000 description 11
- 239000000758 substrate Substances 0.000 description 11
- 108091023037 Aptamer Proteins 0.000 description 10
- 230000000295 complement effect Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 230000004048 modification Effects 0.000 description 9
- 238000012986 modification Methods 0.000 description 9
- 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 8
- 239000000370 acceptor Substances 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 239000001993 wax Substances 0.000 description 8
- 238000007792 addition Methods 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 229910001425 magnesium ion Inorganic materials 0.000 description 6
- 239000002777 nucleoside Substances 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 238000002372 labelling Methods 0.000 description 5
- -1 nucleoside triphosphates Chemical class 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 125000002652 ribonucleotide group Chemical group 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 108010006785 Taq Polymerase Proteins 0.000 description 4
- 229960002685 biotin Drugs 0.000 description 4
- 235000020958 biotin Nutrition 0.000 description 4
- 239000011616 biotin Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000001351 cycling effect Effects 0.000 description 4
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 4
- 238000004925 denaturation Methods 0.000 description 4
- 230000036425 denaturation Effects 0.000 description 4
- 239000000539 dimer Substances 0.000 description 4
- 239000000975 dye Substances 0.000 description 4
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
- 238000009396 hybridization Methods 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 150000003833 nucleoside derivatives Chemical class 0.000 description 4
- 230000037452 priming Effects 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 125000002264 triphosphate group Chemical class [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 4
- 241000713869 Moloney murine leukemia virus Species 0.000 description 3
- 108091028664 Ribonucleotide Proteins 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 108091033319 polynucleotide Proteins 0.000 description 3
- 102000040430 polynucleotide Human genes 0.000 description 3
- 239000002157 polynucleotide Substances 0.000 description 3
- 239000002336 ribonucleotide Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000001226 triphosphate Substances 0.000 description 3
- 235000011178 triphosphate Nutrition 0.000 description 3
- XQCZBXHVTFVIFE-UHFFFAOYSA-N 2-amino-4-hydroxypyrimidine Chemical compound NC1=NC=CC(O)=N1 XQCZBXHVTFVIFE-UHFFFAOYSA-N 0.000 description 2
- WCKQPPQRFNHPRJ-UHFFFAOYSA-N 4-[[4-(dimethylamino)phenyl]diazenyl]benzoic acid Chemical compound C1=CC(N(C)C)=CC=C1N=NC1=CC=C(C(O)=O)C=C1 WCKQPPQRFNHPRJ-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 241000713838 Avian myeloblastosis virus Species 0.000 description 2
- 108090001008 Avidin Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 241000204666 Thermotoga maritima Species 0.000 description 2
- 241000589596 Thermus Species 0.000 description 2
- 108010001244 Tli polymerase Proteins 0.000 description 2
- 108010020713 Tth polymerase Proteins 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 229940104302 cytosine Drugs 0.000 description 2
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 2
- SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 2
- RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 2
- HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 2
- GYOZYWVXFNDGLU-XLPZGREQSA-N dTMP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 GYOZYWVXFNDGLU-XLPZGREQSA-N 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 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
- 239000012634 fragment Substances 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 239000012035 limiting reagent Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- 150000008300 phosphoramidites Chemical class 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000002987 primer (paints) Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 229920002477 rna polymer Polymers 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- OAKPWEUQDVLTCN-NKWVEPMBSA-N 2',3'-Dideoxyadenosine-5-triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1CC[C@@H](CO[P@@](O)(=O)O[P@](O)(=O)OP(O)(O)=O)O1 OAKPWEUQDVLTCN-NKWVEPMBSA-N 0.000 description 1
- AWGBKZRMLNVLAF-UHFFFAOYSA-N 3,5-dibromo-n,2-dihydroxybenzamide Chemical compound ONC(=O)C1=CC(Br)=CC(Br)=C1O AWGBKZRMLNVLAF-UHFFFAOYSA-N 0.000 description 1
- QCPFFGGFHNZBEP-UHFFFAOYSA-N 4,5,6,7-tetrachloro-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 QCPFFGGFHNZBEP-UHFFFAOYSA-N 0.000 description 1
- ZLOIGESWDJYCTF-UHFFFAOYSA-N 4-Thiouridine Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-UHFFFAOYSA-N 0.000 description 1
- ZLOIGESWDJYCTF-XVFCMESISA-N 4-thiouridine Chemical class O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-XVFCMESISA-N 0.000 description 1
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical class BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical class IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 description 1
- WQZIDRAQTRIQDX-UHFFFAOYSA-N 6-carboxy-x-rhodamine Chemical compound OC(=O)C1=CC=C(C([O-])=O)C=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 WQZIDRAQTRIQDX-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 239000007989 BIS-Tris Propane buffer Substances 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241001112695 Clostridiales Species 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- AHCYMLUZIRLXAA-SHYZEUOFSA-N Deoxyuridine 5'-triphosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 AHCYMLUZIRLXAA-SHYZEUOFSA-N 0.000 description 1
- BVTJGGGYKAMDBN-UHFFFAOYSA-N Dioxetane Chemical class C1COO1 BVTJGGGYKAMDBN-UHFFFAOYSA-N 0.000 description 1
- 102000008857 Ferritin Human genes 0.000 description 1
- 108050000784 Ferritin Proteins 0.000 description 1
- 238000008416 Ferritin Methods 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- 108091081548 Palindromic sequence Proteins 0.000 description 1
- 108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 1
- 102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 241000205188 Thermococcus Species 0.000 description 1
- 241000205180 Thermococcus litoralis Species 0.000 description 1
- 241000557720 Thermus brockianus Species 0.000 description 1
- 241000589499 Thermus thermophilus Species 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 241000193758 [Bacillus] caldotenax Species 0.000 description 1
- AZRNEVJSOSKAOC-VPHBQDTQSA-N [[(2r,3s,5r)-5-[5-[(e)-3-[6-[5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]hexanoylamino]prop-1-enyl]-2,4-dioxopyrimidin-1-yl]-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C(\C=C\CNC(=O)CCCCCNC(=O)CCCC[C@H]2[C@H]3NC(=O)N[C@H]3CS2)=C1 AZRNEVJSOSKAOC-VPHBQDTQSA-N 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001745 anti-biotin effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- HHKZCCWKTZRCCL-UHFFFAOYSA-N bis-tris propane Chemical compound OCC(CO)(CO)NCCCNC(CO)(CO)CO HHKZCCWKTZRCCL-UHFFFAOYSA-N 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- CZPLANDPABRVHX-UHFFFAOYSA-N cascade blue Chemical compound C=1C2=CC=CC=C2C(NCC)=CC=1C(C=1C=CC(=CC=1)N(CC)CC)=C1C=CC(=[N+](CC)CC)C=C1 CZPLANDPABRVHX-UHFFFAOYSA-N 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 239000005549 deoxyribonucleoside Substances 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000007849 hot-start PCR Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- ONUFESLQCSAYKA-UHFFFAOYSA-N iprodione Chemical compound O=C1N(C(=O)NC(C)C)CC(=O)N1C1=CC(Cl)=CC(Cl)=C1 ONUFESLQCSAYKA-UHFFFAOYSA-N 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 238000000329 molecular dynamics simulation Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 150000003220 pyrenes Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000033458 reproduction Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- ABZLKHKQJHEPAX-UHFFFAOYSA-N tetramethylrhodamine Chemical compound C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C([O-])=O ABZLKHKQJHEPAX-UHFFFAOYSA-N 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- 238000005382 thermal cycling Methods 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/48—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US45967203P | 2003-04-01 | 2003-04-01 | |
| US60/459,672 | 2003-04-01 | ||
| PCT/US2004/010029 WO2004090153A2 (en) | 2003-04-01 | 2004-04-01 | Polymerase inhibitor and method of using same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2521127A1 CA2521127A1 (en) | 2004-10-21 |
| CA2521127C true CA2521127C (en) | 2014-05-27 |
Family
ID=33159672
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2521127A Expired - Lifetime CA2521127C (en) | 2003-04-01 | 2004-04-01 | Polymerase inhibitor and method of using same |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US7820808B2 (https=) |
| EP (1) | EP1615942B1 (https=) |
| JP (1) | JP4567673B2 (https=) |
| AU (1) | AU2004227353B2 (https=) |
| CA (1) | CA2521127C (https=) |
| WO (1) | WO2004090153A2 (https=) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6830902B1 (en) * | 1999-07-02 | 2004-12-14 | Invitrogen Corporation | Compositions and methods for enhanced sensitivity and specificity of nucleic acid synthesis |
| ATE541055T1 (de) * | 2004-10-18 | 2012-01-15 | Univ Brandeis | Reagenzien und verfahren zur verbesserung der reproduzierbarkeit und zur reduzierung des mispriming bei der pcr-amplifikation |
| US20070212704A1 (en) | 2005-10-03 | 2007-09-13 | Applera Corporation | Compositions, methods, and kits for amplifying nucleic acids |
| US8012694B2 (en) * | 2006-09-14 | 2011-09-06 | Immutopics, Inc. | Assay for the detection of phosphorylated PTH |
| US10865431B1 (en) * | 2008-06-17 | 2020-12-15 | Steven A Benner | Polymerase incorporation of non-standard nucleotides |
| CA2688174C (en) * | 2008-12-19 | 2018-08-07 | F. Hoffmann-La Roche Ag | Dry composition of reaction compounds with stabilized polymerase |
| AU2010224100B2 (en) * | 2009-03-12 | 2015-10-22 | Brandeis University | Reagents and methods for PCR |
| CA2779689A1 (en) * | 2009-11-06 | 2011-05-12 | Enzymatics, Inc. | Composition and method for synthesizing a deoxyribonucleotide chain using a double stranded nucleic acid complex with a thermostable polymerase |
| JP7106461B2 (ja) | 2016-06-07 | 2022-07-26 | セファイド | 熱安定性ポリメラーゼ阻害剤組成物及び方法 |
| GB201611469D0 (en) | 2016-06-30 | 2016-08-17 | Lumiradx Tech Ltd | Improvements in or relating to nucleic acid amplification processes |
| GB2569965A (en) | 2018-01-04 | 2019-07-10 | Lumiradx Uk Ltd | Improvements in or relating to amplification of nucleic acids |
| EP3818170A4 (en) * | 2018-07-02 | 2022-03-09 | Swift Biosciences, Inc. | Temperature controlled dna polymerase inhibitors |
| JP2023531027A (ja) * | 2020-06-22 | 2023-07-20 | ▲蘇▼州新海生物科技股▲ふん▼有限公司 | 核酸リガンド、およびその使用 |
Family Cites Families (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| US5470974A (en) | 1985-03-15 | 1995-11-28 | Neu-Gene Development Group | Uncharged polynucleotide-binding polymers |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US4996143A (en) | 1985-12-23 | 1991-02-26 | Syngene, Inc. | Fluorescent stokes shift probes for polynucleotide hybridization |
| US4800159A (en) | 1986-02-07 | 1989-01-24 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences |
| IL86164A0 (en) | 1987-04-28 | 1988-11-15 | Tamir Biotechnology Ltd | Improved dna probes |
| JPH0344560Y2 (https=) | 1987-08-24 | 1991-09-19 | ||
| WO1989002921A1 (en) | 1987-09-22 | 1989-04-06 | Temple University | Artificial dna base pair analogues |
| US6054270A (en) | 1988-05-03 | 2000-04-25 | Oxford Gene Technology Limited | Analying polynucleotide sequences |
| US6444798B1 (en) | 1988-06-06 | 2002-09-03 | Steven Albert Benner | Chimeras of sulfur-linked oligonucleotide analogs and DNA and RNA |
| GB8827160D0 (en) | 1988-11-21 | 1988-12-29 | Apothekernes Lab | Detection & quantitative determination of rna & dna |
| GB8902689D0 (en) | 1989-02-07 | 1989-03-30 | Ici Plc | Assay method |
| US5856092A (en) | 1989-02-13 | 1999-01-05 | Geneco Pty Ltd | Detection of a nucleic acid sequence or a change therein |
| GB8920097D0 (en) | 1989-09-06 | 1989-10-18 | Ici Plc | Amplification processes |
| US6007984A (en) | 1989-11-01 | 1999-12-28 | Zeneca Limited | Detection of DNA/RNA by fluorescence polarization |
| US5412088A (en) | 1989-11-20 | 1995-05-02 | Rutgers, The State University | 6-O-substituted guanosine derivatives |
| US5693502A (en) | 1990-06-11 | 1997-12-02 | Nexstar Pharmaceuticals, Inc. | Nucleic acid ligand inhibitors to DNA polymerases |
| US5874557A (en) | 1990-06-11 | 1999-02-23 | Nexstar Pharmaceuticals, Inc. | Nucleic acid ligand inhibitors to DNA polymerases |
| US5763173A (en) | 1990-06-11 | 1998-06-09 | Nexstar Pharmaceuticals, Inc. | Nucleic acid ligand inhibitors to DNA polymerases |
| US5552541A (en) | 1990-06-20 | 1996-09-03 | Beckman Instruments, Inc. | Haptenic probes for detecting capture polynucleotides |
| US5177064A (en) | 1990-07-13 | 1993-01-05 | University Of Florida | Targeted drug delivery via phosphonate derivatives |
| US5210015A (en) | 1990-08-06 | 1993-05-11 | Hoffman-La Roche Inc. | Homogeneous assay system using the nuclease activity of a nucleic acid polymerase |
| US6037120A (en) | 1995-10-12 | 2000-03-14 | Benner; Steven Albert | Recognition of oligonucleotides containing non-standard base pairs |
| US5432272A (en) | 1990-10-09 | 1995-07-11 | Benner; Steven A. | Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases |
| US6140496A (en) | 1990-10-09 | 2000-10-31 | Benner; Steven Albert | Precursors for deoxyribonucleotides containing non-standard nucleosides |
| US5965364A (en) | 1990-10-09 | 1999-10-12 | Benner; Steven Albert | Method for selecting functional deoxyribonucleotide derivatives |
| DK0515660T3 (da) | 1990-12-21 | 1997-07-28 | Hoffmann La Roche | HLA-DQbeta-DNA-typebestemmelse |
| DE4129653A1 (de) | 1991-09-06 | 1993-03-11 | Boehringer Mannheim Gmbh | Verfahren zum nachweis aehnlicher nukleinsaeuren |
| US5846717A (en) | 1996-01-24 | 1998-12-08 | Third Wave Technologies, Inc. | Detection of nucleic acid sequences by invader-directed cleavage |
| US5958784A (en) | 1992-03-25 | 1999-09-28 | Benner; Steven Albert | Predicting folded structures of proteins |
| AU3933393A (en) | 1993-03-17 | 1994-10-11 | City Of Hope | Nucleic acid sequences having single stranded ends |
| US6156501A (en) | 1993-10-26 | 2000-12-05 | Affymetrix, Inc. | Arrays of modified nucleic acid probes and methods of use |
| WO1995021271A1 (en) | 1994-02-07 | 1995-08-10 | Molecular Tool, Inc. | Ligase/polymerase-mediated genetic bit analysistm of single nucleotide polymorphisms and its use in genetic analysis |
| US5681702A (en) | 1994-08-30 | 1997-10-28 | Chiron Corporation | Reduction of nonspecific hybridization by using novel base-pairing schemes |
| US5604097A (en) | 1994-10-13 | 1997-02-18 | Spectragen, Inc. | Methods for sorting polynucleotides using oligonucleotide tags |
| US5565340A (en) | 1995-01-27 | 1996-10-15 | Clontech Laboratories, Inc. | Method for suppressing DNA fragment amplification during PCR |
| GB9507238D0 (en) | 1995-04-07 | 1995-05-31 | Isis Innovation | Detecting dna sequence variations |
| US6183967B1 (en) | 1995-06-07 | 2001-02-06 | Nexstar Pharmaceuticals | Nucleic acid ligand inhibitors to DNA polymerases |
| US6020130A (en) | 1995-06-07 | 2000-02-01 | Nexstar Pharmaceuticals, Inc. | Nucleic acid ligands that bind to and inhibit DNA polymerases |
| US5736330A (en) | 1995-10-11 | 1998-04-07 | Luminex Corporation | Method and compositions for flow cytometric determination of DNA sequences |
| US5705621A (en) | 1995-11-17 | 1998-01-06 | Isis Pharmaceuticals, Inc. | Oligomeric phosphite, phosphodiester, Phosphorothioate and phosphorodithioate compounds and intermediates for preparing same |
| WO1997035033A1 (en) | 1996-03-19 | 1997-09-25 | Molecular Tool, Inc. | Method for determining the nucleotide sequence of a polynucleotide |
| US5780233A (en) | 1996-06-06 | 1998-07-14 | Wisconsin Alumni Research Foundation | Artificial mismatch hybridization |
| US6124092A (en) | 1996-10-04 | 2000-09-26 | The Perkin-Elmer Corporation | Multiplex polynucleotide capture methods and compositions |
| US6482590B1 (en) | 1996-12-20 | 2002-11-19 | Aventis Behring Gmbh | Method for polynucleotide amplification |
| US7101672B2 (en) | 1998-05-05 | 2006-09-05 | Third Wave Technologies, Inc. | Target-dependent reactions using structure-bridging oligonucleotides |
| JP4185185B2 (ja) | 1997-05-08 | 2008-11-26 | 征夫 軽部 | 部分二重鎖ｄｎａを利用したｄｎａの検出方法 |
| US5928869A (en) | 1997-05-30 | 1999-07-27 | Becton, Dickinson And Company | Detection of nucleic acids by fluorescence quenching |
| JP4502502B2 (ja) | 1997-10-28 | 2010-07-14 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | フローサイトメトリーを用いるｄｎａ多型の同定方法 |
| GB9725197D0 (en) | 1997-11-29 | 1998-01-28 | Secr Defence | Detection system |
| US6046807A (en) | 1998-05-14 | 2000-04-04 | Luminex Corporation | Diode laser based measurement apparatus |
| EP1090293B2 (en) | 1998-06-24 | 2019-01-23 | Illumina, Inc. | Decoding of array sensors with microspheres |
| US6200757B1 (en) | 1999-01-19 | 2001-03-13 | Dade Behring Inc. | Method for controlling the extension of an oligonucleotide |
| US6274353B1 (en) | 1999-09-22 | 2001-08-14 | Genecopoeia, Inc. | Method and compositions for improved polynucleotide synthesis |
| US6528254B1 (en) | 1999-10-29 | 2003-03-04 | Stratagene | Methods for detection of a target nucleic acid sequence |
| US6509157B1 (en) | 1999-11-05 | 2003-01-21 | Roche Molecular Systems, Inc | 3 blocked nucleic acid amplification primers |
| AU2001229576A1 (en) | 2000-01-15 | 2001-07-24 | Genelabs Technologies, Inc. | Nucleic acid binding site assay and selection method |
| WO2001075139A1 (en) | 2000-04-03 | 2001-10-11 | Biolink Partners, Inc. | Reversible chemical modification of nucleic acids and improved method for nucleic acid hybridization |
| AU7125401A (en) | 2000-05-19 | 2001-12-03 | David J Marshall | Materials and methods for detection of nucleic acids |
| AU1317502A (en) | 2000-10-14 | 2002-04-29 | Eragen Biosciences Inc | Solid support assay systems and methods utilizing non-standard bases |
| EP1456394B2 (en) * | 2001-11-28 | 2011-04-27 | Bio-Rad Laboratories, Inc. | Methods of using improved polymerases |
| US20030194705A1 (en) | 2002-03-01 | 2003-10-16 | Schroth Gary P. | Methods of using unnatural nucleobases for decoding |
| US7282333B2 (en) | 2003-10-20 | 2007-10-16 | Promega Corporation | Methods and compositions for nucleic acid analysis |
-
2004
- 2004-04-01 AU AU2004227353A patent/AU2004227353B2/en not_active Expired
- 2004-04-01 JP JP2006509580A patent/JP4567673B2/ja not_active Expired - Lifetime
- 2004-04-01 WO PCT/US2004/010029 patent/WO2004090153A2/en not_active Ceased
- 2004-04-01 CA CA2521127A patent/CA2521127C/en not_active Expired - Lifetime
- 2004-04-01 EP EP04758726.6A patent/EP1615942B1/en not_active Expired - Lifetime
- 2004-04-01 US US10/551,705 patent/US7820808B2/en active Active
-
2010
- 2010-09-17 US US12/884,575 patent/US8313932B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004090153A2 (en) | 2004-10-21 |
| US7820808B2 (en) | 2010-10-26 |
| CA2521127A1 (en) | 2004-10-21 |
| EP1615942A2 (en) | 2006-01-18 |
| JP4567673B2 (ja) | 2010-10-20 |
| EP1615942A4 (en) | 2009-03-25 |
| AU2004227353A1 (en) | 2004-10-21 |
| US20110104678A1 (en) | 2011-05-05 |
| US8313932B2 (en) | 2012-11-20 |
| WO2004090153A3 (en) | 2005-06-23 |
| US20080108124A1 (en) | 2008-05-08 |
| JP2006521824A (ja) | 2006-09-28 |
| AU2004227353B2 (en) | 2010-02-25 |
| EP1615942B1 (en) | 2016-03-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8313932B2 (en) | Polymerase inhibitor and method of using same | |
| US9447457B2 (en) | Detection of target nucleic acid sequences by cyclic exonucleolytic reactions | |
| US9657340B2 (en) | Isothermal nucleic acid amplification | |
| US7727722B2 (en) | Ligation amplification | |
| JP2004532615A (ja) | 核酸の検出および識別のためのプライマーおよび方法 | |
| US20130302794A1 (en) | Nucleic acid detection by oligonucleotide probes cleaved by both exonuclease and endonuclease | |
| US20120219945A1 (en) | Use of single-stranded binding protein in amplifying target nucleic acid | |
| CN105705660B (zh) | 使用重叠引物和熔解探针检测单核苷酸多态性 | |
| JP2025532123A (ja) | Ｒｎａｓｅｈ２を用いて活性化したユニバーサル蛍光プローブ | |
| EP3559273A1 (en) | Cobra probes to detect a marker for epidemic ribotypes of clostridium difficile | |
| EP3497227A2 (en) | Rnase h mutants in an emulsion | |
| KR101757473B1 (ko) | ｈＣＴＯ를 이용하는 ＰＴＯ 절단 및 연장 분석에 의한 고상에서의 타겟 핵산 서열 검출 | |
| JP2005052143A (ja) | ホットスタートリアルタイムポリメラーゼ連鎖反応のための新しい検出形式 | |
| US20130177906A1 (en) | Enhanced amplification of target nucleic acid | |
| EP3765479B1 (en) | Quantitative amplification normalization with quenchers | |
| EP1550717A1 (en) | Novel method of assyaing nucleic acid using labeled nucleotide | |
| CN115943217B (zh) | 一种用于分析靶多核苷酸的序列的方法 | |
| US20130209987A1 (en) | Oligonucleotide sets for detection of human papillomavirus | |
| US9260746B2 (en) | Photoinduced electron transfer (PET) primer for nucleic acid amplification |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |
Effective date: 20240402 |