CN102443030B - 光可断裂的标记核苷酸和核苷与标记的核苷酸和核苷以及其在dna测序中的使用方法 - Google Patents
光可断裂的标记核苷酸和核苷与标记的核苷酸和核苷以及其在dna测序中的使用方法 Download PDFInfo
- Publication number
- CN102443030B CN102443030B CN201110376726.1A CN201110376726A CN102443030B CN 102443030 B CN102443030 B CN 102443030B CN 201110376726 A CN201110376726 A CN 201110376726A CN 102443030 B CN102443030 B CN 102443030B
- Authority
- CN
- China
- Prior art keywords
- compound
- further defined
- solution
- nitrophenyl
- nucleotide
- 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.)
- Active
Links
- 125000003729 nucleotide group Chemical group 0.000 title claims abstract description 110
- 239000002773 nucleotide Substances 0.000 title claims abstract description 101
- 239000002777 nucleoside Substances 0.000 title claims abstract description 90
- 125000003835 nucleoside group Chemical group 0.000 title claims abstract description 51
- 238000000034 method Methods 0.000 title claims description 128
- 238000001712 DNA sequencing Methods 0.000 title abstract description 25
- 239000007850 fluorescent dye Substances 0.000 claims abstract description 16
- 230000006820 DNA synthesis Effects 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims description 287
- 239000000203 mixture Substances 0.000 claims description 138
- 229910019142 PO4 Inorganic materials 0.000 claims description 91
- 239000010452 phosphate Substances 0.000 claims description 91
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 89
- 150000007523 nucleic acids Chemical class 0.000 claims description 63
- 239000000975 dye Substances 0.000 claims description 59
- 239000007787 solid Substances 0.000 claims description 58
- 108020004707 nucleic acids Proteins 0.000 claims description 51
- 102000039446 nucleic acids Human genes 0.000 claims description 51
- 238000005259 measurement Methods 0.000 claims description 49
- 238000006243 chemical reaction Methods 0.000 claims description 47
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 claims description 35
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 claims description 35
- 229910052799 carbon Inorganic materials 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 238000006911 enzymatic reaction Methods 0.000 claims description 17
- 102000004190 Enzymes Human genes 0.000 claims description 16
- 108090000790 Enzymes Proteins 0.000 claims description 16
- 238000012163 sequencing technique Methods 0.000 claims description 16
- 125000005340 bisphosphate group Chemical group 0.000 claims description 13
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 claims description 12
- 230000004048 modification Effects 0.000 claims description 10
- 238000012986 modification Methods 0.000 claims description 10
- 235000021251 pulses Nutrition 0.000 claims description 9
- 238000001514 detection method Methods 0.000 claims description 8
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 8
- 238000003384 imaging method Methods 0.000 claims description 7
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 claims description 6
- 238000006555 catalytic reaction Methods 0.000 claims description 6
- 239000000470 constituent Substances 0.000 claims description 6
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 claims description 6
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 claims description 6
- 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 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 230000000977 initiatory effect Effects 0.000 claims description 6
- QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 claims description 6
- 239000006225 natural substrate Substances 0.000 claims description 6
- 238000001668 nucleic acid synthesis Methods 0.000 claims description 6
- IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 claims description 6
- 108060006184 phycobiliprotein Proteins 0.000 claims description 6
- 238000012797 qualification Methods 0.000 claims description 6
- 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 claims description 6
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 108010006785 Taq Polymerase Proteins 0.000 claims description 4
- 235000011180 diphosphates Nutrition 0.000 claims description 4
- 238000009396 hybridization Methods 0.000 claims description 3
- 230000002103 transcriptional effect Effects 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 238000005516 engineering process Methods 0.000 abstract description 22
- 238000004458 analytical method Methods 0.000 abstract description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 292
- 239000000243 solution Substances 0.000 description 230
- -1 2-nitrobenzyl Chemical group 0.000 description 148
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 141
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 114
- 238000003756 stirring Methods 0.000 description 113
- 229940048102 triphosphoric acid Drugs 0.000 description 107
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 94
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
- 230000015572 biosynthetic process Effects 0.000 description 87
- 238000010898 silica gel chromatography Methods 0.000 description 87
- 238000003786 synthesis reaction Methods 0.000 description 87
- 239000011734 sodium Substances 0.000 description 80
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 78
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 58
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 57
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 52
- 239000006260 foam Substances 0.000 description 48
- 239000012141 concentrate Substances 0.000 description 46
- 102000016911 Deoxyribonucleases Human genes 0.000 description 39
- 108010053770 Deoxyribonucleases Proteins 0.000 description 39
- 229940109357 desoxyribonuclease Drugs 0.000 description 39
- 238000001269 time-of-flight mass spectrometry Methods 0.000 description 39
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 36
- 230000005284 excitation Effects 0.000 description 33
- 239000002253 acid Substances 0.000 description 32
- BZTDTCNHAFUJOG-UHFFFAOYSA-N 6-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C11OC(=O)C2=CC=C(C(=O)O)C=C21 BZTDTCNHAFUJOG-UHFFFAOYSA-N 0.000 description 31
- 239000011541 reaction mixture Substances 0.000 description 30
- 239000012071 phase Substances 0.000 description 29
- 238000013016 damping Methods 0.000 description 28
- 239000012530 fluid Substances 0.000 description 28
- 239000012044 organic layer Substances 0.000 description 28
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 27
- 239000007853 buffer solution Substances 0.000 description 27
- AFQIYTIJXGTIEY-UHFFFAOYSA-N hydrogen carbonate;triethylazanium Chemical compound OC(O)=O.CCN(CC)CC AFQIYTIJXGTIEY-UHFFFAOYSA-N 0.000 description 27
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 27
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 27
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 26
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 26
- 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 25
- 238000004108 freeze drying Methods 0.000 description 25
- 230000002441 reversible effect Effects 0.000 description 25
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 24
- 108020004414 DNA Proteins 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- 125000005767 propoxymethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])[#8]C([H])([H])* 0.000 description 22
- GAUSMJHDHCSZOX-UHFFFAOYSA-N 2,2,2-trifluoro-n-prop-2-ynylacetamide Chemical compound FC(F)(F)C(=O)NCC#C GAUSMJHDHCSZOX-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 238000004128 high performance liquid chromatography Methods 0.000 description 21
- 238000004679 31P NMR spectroscopy Methods 0.000 description 20
- IDLISIVVYLGCKO-UHFFFAOYSA-N 6-carboxy-4',5'-dichloro-2',7'-dimethoxyfluorescein Chemical compound O1C(=O)C2=CC=C(C(O)=O)C=C2C21C1=CC(OC)=C(O)C(Cl)=C1OC1=C2C=C(OC)C(O)=C1Cl IDLISIVVYLGCKO-UHFFFAOYSA-N 0.000 description 20
- 230000008033 biological extinction Effects 0.000 description 20
- 150000002460 imidazoles Chemical class 0.000 description 20
- 239000012299 nitrogen atmosphere Substances 0.000 description 20
- 230000003287 optical effect Effects 0.000 description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 20
- 229920006395 saturated elastomer Polymers 0.000 description 20
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 20
- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
- 238000005571 anion exchange chromatography Methods 0.000 description 19
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 19
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 18
- 238000000862 absorption spectrum Methods 0.000 description 17
- 238000010511 deprotection reaction Methods 0.000 description 17
- 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 description 16
- 238000001035 drying Methods 0.000 description 16
- 238000000746 purification Methods 0.000 description 16
- 238000004007 reversed phase HPLC Methods 0.000 description 16
- 0 CC(c(cc1)ccc1C#CCNC(c1ccc([*-])c(C(c(ccc(O)c2)c2O2)=C(C=C3)C2=CC3=O)c1)=O)Nc1ncnc2c1nc[n]2CC(CO[C@]1COP(OC)(OP(O)(OP(O)(OC)=O)=O)=O)=C1O Chemical compound CC(c(cc1)ccc1C#CCNC(c1ccc([*-])c(C(c(ccc(O)c2)c2O2)=C(C=C3)C2=CC3=O)c1)=O)Nc1ncnc2c1nc[n]2CC(CO[C@]1COP(OC)(OP(O)(OP(O)(OC)=O)=O)=O)=C1O 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 14
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 14
- 239000000908 ammonium hydroxide Substances 0.000 description 14
- 238000013459 approach Methods 0.000 description 14
- 125000003118 aryl group Chemical group 0.000 description 14
- 229940088598 enzyme Drugs 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 13
- 229940104302 cytosine Drugs 0.000 description 13
- 125000006239 protecting group Chemical group 0.000 description 13
- VDABVNMGKGUPEY-UHFFFAOYSA-N 6-carboxyfluorescein succinimidyl ester Chemical compound C=1C(O)=CC=C2C=1OC1=CC(O)=CC=C1C2(C1=C2)OC(=O)C1=CC=C2C(=O)ON1C(=O)CCC1=O VDABVNMGKGUPEY-UHFFFAOYSA-N 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
- 210000001541 thymus gland Anatomy 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- HXBMIQJOSHZCFX-UHFFFAOYSA-N 1-(bromomethyl)-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1CBr HXBMIQJOSHZCFX-UHFFFAOYSA-N 0.000 description 10
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 10
- 125000001624 naphthyl group Chemical group 0.000 description 10
- 229910052760 oxygen Inorganic materials 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 10
- PCDQPRRSZKQHHS-XVFCMESISA-N CTP Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 PCDQPRRSZKQHHS-XVFCMESISA-N 0.000 description 9
- 229910004298 SiO 2 Inorganic materials 0.000 description 9
- 239000012298 atmosphere Substances 0.000 description 9
- 238000004140 cleaning Methods 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- UUVBVONAGUSCCH-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4',5'-dichloro-3',6'-dihydroxy-2',7'-dimethoxy-1-oxospiro[2-benzofuran-3,9'-xanthene]-5-carboxylate Chemical compound ClC1=C(O)C(OC)=CC2=C1OC1=C(Cl)C(O)=C(OC)C=C1C2(C1=C2)OC(=O)C1=CC=C2C(=O)ON1C(=O)CCC1=O UUVBVONAGUSCCH-UHFFFAOYSA-N 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- 150000001335 aliphatic alkanes Chemical class 0.000 description 8
- 125000000304 alkynyl group Chemical group 0.000 description 8
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 229960004756 ethanol Drugs 0.000 description 8
- 125000004494 ethyl ester group Chemical group 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 8
- 125000003367 polycyclic group Chemical group 0.000 description 8
- 150000004291 polyenes Chemical class 0.000 description 8
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 8
- 239000002342 ribonucleoside Substances 0.000 description 8
- 125000002769 thiazolinyl group Chemical group 0.000 description 8
- 235000011178 triphosphate Nutrition 0.000 description 8
- 239000001226 triphosphate Substances 0.000 description 8
- 230000004913 activation Effects 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 230000001588 bifunctional effect Effects 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 229910052740 iodine Inorganic materials 0.000 description 7
- 239000011630 iodine Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 7
- 239000012266 salt solution Substances 0.000 description 7
- 229940045145 uridine Drugs 0.000 description 7
- 239000011782 vitamin Substances 0.000 description 7
- 229940088594 vitamin Drugs 0.000 description 7
- 229930003231 vitamin Natural products 0.000 description 7
- 235000013343 vitamin Nutrition 0.000 description 7
- 150000003722 vitamin derivatives Chemical class 0.000 description 7
- JAPYIBBSTJFDAK-UHFFFAOYSA-N 2,4,6-tri(propan-2-yl)benzenesulfonyl chloride Chemical compound CC(C)C1=CC(C(C)C)=C(S(Cl)(=O)=O)C(C(C)C)=C1 JAPYIBBSTJFDAK-UHFFFAOYSA-N 0.000 description 6
- 229930024421 Adenine Natural products 0.000 description 6
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 6
- OIRDTQYFTABQOQ-KQYNXXCUSA-N Adenosine Natural products C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 6
- 229960000643 adenine Drugs 0.000 description 6
- 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 6
- 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 6
- 230000000694 effects Effects 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 125000005647 linker group Chemical group 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- 239000002808 molecular sieve Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 6
- 229940104230 thymidine Drugs 0.000 description 6
- 238000004448 titration Methods 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- DSDBYQDNNWCLHL-UHFFFAOYSA-N 1-(2-nitrophenyl)ethanol Chemical compound CC(O)C1=CC=CC=C1[N+]([O-])=O DSDBYQDNNWCLHL-UHFFFAOYSA-N 0.000 description 5
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 5
- MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 5
- 230000006837 decompression Effects 0.000 description 5
- MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- BWRBVBFLFQKBPT-UHFFFAOYSA-N (2-nitrophenyl)methanol Chemical compound OCC1=CC=CC=C1[N+]([O-])=O BWRBVBFLFQKBPT-UHFFFAOYSA-N 0.000 description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- MSWZFWKMSRAUBD-UHFFFAOYSA-N 2-Amino-2-Deoxy-Hexose Chemical compound NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 4
- COCMHKNAGZHBDZ-UHFFFAOYSA-N 4-carboxy-3-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]benzoate Chemical compound C=12C=CC(=[N+](C)C)C=C2OC2=CC(N(C)C)=CC=C2C=1C1=CC(C([O-])=O)=CC=C1C(O)=O COCMHKNAGZHBDZ-UHFFFAOYSA-N 0.000 description 4
- 239000004342 Benzoyl peroxide Substances 0.000 description 4
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 4
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 4
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 4
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 4
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 4
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 108091028664 Ribonucleotide Proteins 0.000 description 4
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 4
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 229960005305 adenosine Drugs 0.000 description 4
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 4
- 235000019400 benzoyl peroxide Nutrition 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000005549 deoxyribonucleoside Substances 0.000 description 4
- 239000012973 diazabicyclooctane Substances 0.000 description 4
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 229930182470 glycoside Natural products 0.000 description 4
- 150000002338 glycosides Chemical class 0.000 description 4
- 229940029575 guanosine Drugs 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 150000003014 phosphoric acid esters Chemical class 0.000 description 4
- 238000006116 polymerization reaction Methods 0.000 description 4
- 238000002953 preparative HPLC Methods 0.000 description 4
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 4
- 239000002336 ribonucleotide Substances 0.000 description 4
- 125000002652 ribonucleotide group Chemical group 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 235000009518 sodium iodide Nutrition 0.000 description 4
- 229960002317 succinimide Drugs 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 4
- LKEXBDWKOKZZAB-UHFFFAOYSA-N 1-(bromomethyl)-4-iodo-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(I)=CC=C1CBr LKEXBDWKOKZZAB-UHFFFAOYSA-N 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- PVJZBZSCGJAWNG-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonyl chloride Chemical compound CC1=CC(C)=C(S(Cl)(=O)=O)C(C)=C1 PVJZBZSCGJAWNG-UHFFFAOYSA-N 0.000 description 3
- 125000003456 2,6-dinitrophenyl group Chemical group [H]C1=C([H])C(=C(*)C(=C1[H])[N+]([O-])=O)[N+]([O-])=O 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000001502 gel electrophoresis Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000001360 synchronised effect Effects 0.000 description 3
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 3
- 238000000825 ultraviolet detection Methods 0.000 description 3
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 3
- 229910052727 yttrium Inorganic materials 0.000 description 3
- BXBWYASMNRMGOF-FILYFMJVSA-N (2R,3S,5R)-5-[6-amino-6-[(2-nitrophenyl)methyl]-8H-purin-9-yl]-2-(hydroxymethyl)oxolan-3-ol Chemical compound [N+](=O)([O-])C1=C(CC2(C3=NCN([C@H]4C[C@H](O)[C@@H](CO)O4)C3=NC=N2)N)C=CC=C1 BXBWYASMNRMGOF-FILYFMJVSA-N 0.000 description 2
- RPWNMXPROMWYKP-WBALYPMMSA-N (2R,3S,5R)-5-[6-amino-6-[1-(4-iodophenyl)ethyl]-8H-purin-9-yl]-2-(hydroxymethyl)oxolan-3-ol Chemical compound IC1=CC=C(C=C1)C(C)C1(C2=NCN([C@H]3C[C@H](O)[C@@H](CO)O3)C2=NC=N1)N RPWNMXPROMWYKP-WBALYPMMSA-N 0.000 description 2
- BQTRMYJYYNQQGK-UHFFFAOYSA-N 1-(bromomethyl)-4-iodobenzene Chemical compound BrCC1=CC=C(I)C=C1 BQTRMYJYYNQQGK-UHFFFAOYSA-N 0.000 description 2
- XEQNWUPODWCTAB-RRFJBIMHSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[(2-nitrophenyl)methoxymethyl]pyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(COCC=2C(=CC=CC=2)[N+]([O-])=O)=C1 XEQNWUPODWCTAB-RRFJBIMHSA-N 0.000 description 2
- CBVVPMRIKQTBHA-PXVVHIOLSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[1-(2-nitrophenyl)ethoxymethyl]pyrimidine-2,4-dione Chemical compound C=1C=CC=C([N+]([O-])=O)C=1C(C)OCC(C(NC1=O)=O)=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 CBVVPMRIKQTBHA-PXVVHIOLSA-N 0.000 description 2
- LCMGQMHLQBFEOQ-LNAREIQUSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[[2-methyl-1-(2-nitrophenyl)propoxy]methyl]pyrimidine-2,4-dione Chemical compound C=1C=CC=C([N+]([O-])=O)C=1C(C(C)C)OCC(C(NC1=O)=O)=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 LCMGQMHLQBFEOQ-LNAREIQUSA-N 0.000 description 2
- OSQFQCSVKRFRDG-RRFJBIMHSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-3-[(2-nitrophenyl)methyl]pyrimidine-2,4-dione Chemical compound O=C1N(CC=2C(=CC=CC=2)[N+]([O-])=O)C(=O)C(C)=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 OSQFQCSVKRFRDG-RRFJBIMHSA-N 0.000 description 2
- WSDPMJFJFGPSPV-XUVXKRRUSA-N 1-[(2r,4s,5r)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-hydroxyoxolan-2-yl]-5-methyl-3-[(2-nitrophenyl)methyl]pyrimidine-2,4-dione Chemical compound O=C1N(CC=2C(=CC=CC=2)[N+]([O-])=O)C(=O)C(C)=CN1[C@H]1C[C@H](O)[C@@H](CO[Si](C)(C)C(C)(C)C)O1 WSDPMJFJFGPSPV-XUVXKRRUSA-N 0.000 description 2
- IJWIJLIIOKZJMS-YNEHKIRRSA-N 1-[(2r,4s,5r)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO[Si](C)(C)C(C)(C)C)[C@@H](O)C1 IJWIJLIIOKZJMS-YNEHKIRRSA-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 2
- PAOQTZWNYMMSEE-UHFFFAOYSA-N 2-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]-4-(2,5-dioxopyrrolidin-1-yl)oxycarbonylbenzoate Chemical compound C=12C=CC(=[N+](C)C)C=C2OC2=CC(N(C)C)=CC=C2C=1C(C(=CC=1)C([O-])=O)=CC=1C(=O)ON1C(=O)CCC1=O PAOQTZWNYMMSEE-UHFFFAOYSA-N 0.000 description 2
- NUIHQWAWDWCFML-UHFFFAOYSA-N 2-methyl-1-(2-nitrophenyl)propan-1-ol Chemical compound CC(C)C(O)C1=CC=CC=C1[N+]([O-])=O NUIHQWAWDWCFML-UHFFFAOYSA-N 0.000 description 2
- SLJLYOWDOMBNEX-CGEWXTDFSA-N 4-amino-1-[(2S,3R,4S,5R)-2-[tert-butyl(dimethyl)silyl]-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound CC(C)(C)[Si](C)(C)[C@@]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C(=O)N=C(N)C=C1 SLJLYOWDOMBNEX-CGEWXTDFSA-N 0.000 description 2
- OLXZPDWKRNYJJZ-UHFFFAOYSA-N 5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical compound C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(CO)O1 OLXZPDWKRNYJJZ-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
- BNPOJMWZAZEJTF-WFSWZMDOSA-N 9-[(2R,4S,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-6-[1-(4-iodophenyl)ethyl]-8H-purin-6-amine Chemical compound IC1=CC=C(C=C1)C(C)C1(C2=NCN([C@H]3C[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](CO[Si](C)(C)C(C)(C)C)O3)C2=NC=N1)N BNPOJMWZAZEJTF-WFSWZMDOSA-N 0.000 description 2
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 2
- 125000006414 CCl Chemical group ClC* 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229910020366 ClO 4 Inorganic materials 0.000 description 2
- 208000036693 Color-vision disease Diseases 0.000 description 2
- 208000028782 Hereditary disease Diseases 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 208000024556 Mendelian disease Diseases 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 101150003085 Pdcl gene Proteins 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- XPKHLLVXAOCXPI-AHHOBRAOSA-N [Si](C)(C)(C(C)(C)C)[C@@]1(C[C@@H](O[C@@H]1C(O)[Si](C)(C)C(C)(C)C)N1C(=O)NC(=O)C(=C1)COC(C)C1=C(C=CC=C1)[N+](=O)[O-])O Chemical compound [Si](C)(C)(C(C)(C)C)[C@@]1(C[C@@H](O[C@@H]1C(O)[Si](C)(C)C(C)(C)C)N1C(=O)NC(=O)C(=C1)COC(C)C1=C(C=CC=C1)[N+](=O)[O-])O XPKHLLVXAOCXPI-AHHOBRAOSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
- 125000006278 bromobenzyl group Chemical group 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 201000007254 color blindness Diseases 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 238000013329 compounding Methods 0.000 description 2
- 230000001351 cycling effect Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000006575 electron-withdrawing group Chemical group 0.000 description 2
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- AKRYBBWYDSDZHG-UHFFFAOYSA-N nitrosobis(2-oxopropyl)amine Chemical compound CC(=O)CN(N=O)CC(C)=O AKRYBBWYDSDZHG-UHFFFAOYSA-N 0.000 description 2
- 230000005257 nucleotidylation Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000037452 priming Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- LBEDJOVDXTYGNR-OZHORNFVSA-N tert-butyl 9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[(2-methylpropan-2-yl)oxycarbonylamino]-8H-purine-6-carboxylate Chemical compound C(C)(C)(C)OC(=O)C1(C2=NCN([C@H]3C[C@H](O)[C@@H](CO)O3)C2=NC=N1)NC(=O)OC(C)(C)C LBEDJOVDXTYGNR-OZHORNFVSA-N 0.000 description 2
- IDBGVXWFWLJMPS-MUZRBFGKSA-N tert-butyl 9-[(2R,4S,5R)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-[(2-nitrophenyl)methoxy]oxolan-2-yl]-6-[(2-methylpropan-2-yl)oxycarbonylamino]-8H-purine-6-carboxylate Chemical compound C(C)(C)(C)OC(=O)C1(C2=NCN([C@H]3C[C@H](OCC4=C(C=CC=C4)[N+](=O)[O-])[C@@H](CO[Si](C)(C)C(C)(C)C)O3)C2=NC=N1)NC(=O)OC(C)(C)C IDBGVXWFWLJMPS-MUZRBFGKSA-N 0.000 description 2
- HHMKYPDUKPYANR-DXHLIAITSA-N tert-butyl 9-[(2R,4S,5R)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-hydroxyoxolan-2-yl]-6-[(2-methylpropan-2-yl)oxycarbonylamino]-8H-purine-6-carboxylate Chemical compound C(C)(C)(C)OC(=O)C1(C2=NCN([C@H]3C[C@H](O)[C@@H](CO[Si](C)(C)C(C)(C)C)O3)C2=NC=N1)NC(=O)OC(C)(C)C HHMKYPDUKPYANR-DXHLIAITSA-N 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- RJJQAQFECPHEIJ-FILYFMJVSA-N (2R,3S,5R)-5-(6-amino-6-benzyl-8H-purin-9-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical compound N1=CN=C2N([C@@H]3O[C@H](CO)[C@@H](O)C3)CN=C2C1(N)CC1=CC=CC=C1 RJJQAQFECPHEIJ-FILYFMJVSA-N 0.000 description 1
- SOUTUOOXMGEIST-WBALYPMMSA-N (2R,3S,5R)-5-[6-amino-6-[1-(2-nitrophenyl)ethyl]-8H-purin-9-yl]-2-(hydroxymethyl)oxolan-3-ol Chemical compound [N+](=O)([O-])C1=C(C=CC=C1)C(C)C1(C2=NCN([C@H]3C[C@H](O)[C@@H](CO)O3)C2=NC=N1)N SOUTUOOXMGEIST-WBALYPMMSA-N 0.000 description 1
- QJDFQDBWBVTRBK-MOBHLTHFSA-N (2r,3s,5r)-2-(hydroxymethyl)-5-[6-[1-(2-nitrophenyl)ethylamino]purin-9-yl]oxolan-3-ol Chemical compound C=1C=CC=C([N+]([O-])=O)C=1C(C)NC(C=1N=C2)=NC=NC=1N2[C@H]1C[C@H](O)[C@@H](CO)O1 QJDFQDBWBVTRBK-MOBHLTHFSA-N 0.000 description 1
- RYCCADPMEVLUGZ-VWZUFWLJSA-N (2r,3s,5r)-5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol;diphosphono hydrogen phosphate Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O.C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 RYCCADPMEVLUGZ-VWZUFWLJSA-N 0.000 description 1
- NIMQVHDXSYNJJX-BFHYXJOUSA-N (2r,3s,5r)-5-[6-(benzylamino)purin-9-yl]-2-(hydroxymethyl)oxolan-3-ol Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(NCC=3C=CC=CC=3)=C2N=C1 NIMQVHDXSYNJJX-BFHYXJOUSA-N 0.000 description 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- SUGXZLKUDLDTKX-UHFFFAOYSA-N 1-(2-nitrophenyl)ethanone Chemical compound CC(=O)C1=CC=CC=C1[N+]([O-])=O SUGXZLKUDLDTKX-UHFFFAOYSA-N 0.000 description 1
- NOMYCKVOFCYYEW-RRFJBIMHSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[(4-iodo-2-nitrophenyl)methoxymethyl]pyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(COCC=2C(=CC(I)=CC=2)[N+]([O-])=O)=C1 NOMYCKVOFCYYEW-RRFJBIMHSA-N 0.000 description 1
- CVOFKRWYWCSDMA-UHFFFAOYSA-N 2-chloro-n-(2,6-diethylphenyl)-n-(methoxymethyl)acetamide;2,6-dinitro-n,n-dipropyl-4-(trifluoromethyl)aniline Chemical compound CCC1=CC=CC(CC)=C1N(COC)C(=O)CCl.CCCN(CCC)C1=C([N+]([O-])=O)C=C(C(F)(F)F)C=C1[N+]([O-])=O CVOFKRWYWCSDMA-UHFFFAOYSA-N 0.000 description 1
- OYNHFTGJPVDHNG-SJZRPTKZSA-N 6-amino-3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[1-(2-nitrophenyl)ethyl]-1H-pyrimidin-2-one Chemical compound [N+](=O)([O-])C1=C(C=CC=C1)C(C)C1(NC(N([C@H]2[C@H](O)[C@H](O)[C@@H](CO)O2)C=C1)=O)N OYNHFTGJPVDHNG-SJZRPTKZSA-N 0.000 description 1
- FUFCYEMCAZMTSU-IPMKNSEASA-N 9-[(2r,4s,5r)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-[(2-nitrophenyl)methoxy]oxolan-2-yl]purin-6-amine Chemical compound O([C@H]1C[C@@H](O[C@@H]1CO[Si](C)(C)C(C)(C)C)N1C2=NC=NC(N)=C2N=C1)CC1=CC=CC=C1[N+]([O-])=O FUFCYEMCAZMTSU-IPMKNSEASA-N 0.000 description 1
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 1
- JDWAEQVIVCCPBL-UHFFFAOYSA-O CC(CC(c(cccc1)c1N=O)OCC1=CN(C(C2)OC(CO)C2O)C(C)NC1=O)[PH3+] Chemical compound CC(CC(c(cccc1)c1N=O)OCC1=CN(C(C2)OC(CO)C2O)C(C)NC1=O)[PH3+] JDWAEQVIVCCPBL-UHFFFAOYSA-O 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 108091036333 Rapid DNA Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FBEHPMNCKUQUFR-BFHYXJOUSA-N [(2r,3s,5r)-5-(6-aminopurin-9-yl)-3-[(2-nitrophenyl)methoxy]oxolan-2-yl]methanol Chemical compound O([C@H]1C[C@@H](O[C@@H]1CO)N1C=2N=CN=C(C=2N=C1)N)CC1=CC=CC=C1[N+]([O-])=O FBEHPMNCKUQUFR-BFHYXJOUSA-N 0.000 description 1
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 description 1
- GWBBFXWEJPCIIJ-BFHYXJOUSA-N [[(2r,3s,5r)-5-(6-aminopurin-9-yl)-3-[(2-nitrophenyl)methoxy]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O([C@H]1C[C@@H](O[C@@H]1COP(O)(=O)OP(O)(=O)OP(O)(O)=O)N1C=2N=CN=C(C=2N=C1)N)CC1=CC=CC=C1[N+]([O-])=O GWBBFXWEJPCIIJ-BFHYXJOUSA-N 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- XKRFYHLGVUSROY-UHFFFAOYSA-N argon Substances [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 229960000846 camphor Drugs 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 239000005546 dideoxynucleotide Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 230000005670 electromagnetic radiation Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 150000003948 formamides Chemical class 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 229910052743 krypton Inorganic materials 0.000 description 1
- DNNSSWSSYDEUBZ-UHFFFAOYSA-N krypton atom Chemical compound [Kr] DNNSSWSSYDEUBZ-UHFFFAOYSA-N 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 125000002796 nucleotidyl group Chemical group 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000001327 prunus amygdalus amara l. extract Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 238000007480 sanger sequencing Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 238000011451 sequencing strategy Methods 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 108010068698 spleen exonuclease Proteins 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 1
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/567,193 US7893227B2 (en) | 2006-12-05 | 2006-12-05 | 3′-OH unblocked nucleotides and nucleosides base modified with non-cleavable, terminating groups and methods for their use in DNA sequencing |
| US11/567,189 | 2006-12-05 | ||
| US11/567,189 US7897737B2 (en) | 2006-12-05 | 2006-12-05 | 3′-OH unblocked, nucleotides and nucleosides, base modified with photocleavable, terminating groups and methods for their use in DNA sequencing |
| US11/567,193 | 2006-12-05 | ||
| CN200780049437.2A CN101636406A (zh) | 2006-12-05 | 2007-12-05 | 光可断裂的标记核苷酸和核苷与标记的核苷酸和核苷以及其在dna测序中的使用方法 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200780049437.2A Division CN101636406A (zh) | 2006-12-05 | 2007-12-05 | 光可断裂的标记核苷酸和核苷与标记的核苷酸和核苷以及其在dna测序中的使用方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102443030A CN102443030A (zh) | 2012-05-09 |
| CN102443030B true CN102443030B (zh) | 2015-12-16 |
Family
ID=39493724
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110376726.1A Active CN102443030B (zh) | 2006-12-05 | 2007-12-05 | 光可断裂的标记核苷酸和核苷与标记的核苷酸和核苷以及其在dna测序中的使用方法 |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP2125856B1 (https=) |
| JP (1) | JP5513122B2 (https=) |
| KR (1) | KR101504640B1 (https=) |
| CN (1) | CN102443030B (https=) |
| AU (1) | AU2007329361B2 (https=) |
| BR (1) | BRPI0719923B1 (https=) |
| CA (1) | CA2670937C (https=) |
| IL (1) | IL199051A (https=) |
| MX (2) | MX338089B (https=) |
| NZ (1) | NZ577303A (https=) |
| RU (1) | RU2009121089A (https=) |
| WO (1) | WO2008070749A2 (https=) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7897737B2 (en) | 2006-12-05 | 2011-03-01 | Lasergen, Inc. | 3′-OH unblocked, nucleotides and nucleosides, base modified with photocleavable, terminating groups and methods for their use in DNA sequencing |
| NZ590265A (en) | 2008-06-11 | 2012-11-30 | Lasergen Inc | Nucleotides and nucleosides and methods for their use in dna sequencing |
| EP2321429B1 (en) | 2008-09-03 | 2016-08-17 | Quantumdx Group Limited | Methods and kits for nucleic acid sequencing |
| US10759824B2 (en) | 2008-09-03 | 2020-09-01 | Quantumdx Group Limited | Design, synthesis and use of synthetic nucleotides comprising charge mass tags |
| WO2013040257A1 (en) | 2011-09-13 | 2013-03-21 | Lasergen, Inc. | 5-methoxy. 3'-oh unblocked, fast photocleavable terminating nucleotides and methods for nucleic acid sequencing |
| WO2013105025A1 (en) * | 2012-01-13 | 2013-07-18 | Koninklijke Philips N.V. | Dna sequencing with reagent recycling on wiregrid |
| CN103602719B (zh) * | 2013-04-07 | 2016-06-08 | 北京迈基诺基因科技有限责任公司 | 一种基因测序方法 |
| WO2015015913A1 (ja) * | 2013-07-31 | 2015-02-05 | 株式会社 日立ハイテクノロジーズ | 核酸分析用フローセル、及び核酸分析装置 |
| GB201414098D0 (en) | 2014-08-08 | 2014-09-24 | Illumina Cambridge Ltd | Modified nucleotide linkers |
| RU2582198C1 (ru) * | 2014-11-20 | 2016-04-20 | Федеральное государственное бюджетное учреждение науки Лимнологический институт Сибирского отделения Российской академии наук (ЛИН СО РАН) | Аналоги природных дезоксирибонуклеозидтрифосфатов и рибонуклеозидтрифосфатов, содержащие репортёрные флуоресцентные группы, для использования в аналитической биоорганической химии |
| CN105001292A (zh) * | 2015-07-14 | 2015-10-28 | 深圳市瀚海基因生物科技有限公司 | 一种光可断裂的荧光标记可逆终端化合物及其在dna或rna测序中的用途 |
| EP3400444A4 (en) | 2016-01-04 | 2019-10-16 | QuantuMDx Group Limited | DESIGN, SYNTHESIS AND USE OF SYNTHETIC NUCLEOTIDES WITH LOADING MASS MARKINGS |
| GB201711219D0 (en) | 2017-07-12 | 2017-08-23 | Illumina Cambridge Ltd | Short pendant arm linkers for nucleotides in sequencing applications |
| CN113272443B (zh) | 2019-01-07 | 2025-01-10 | 安捷伦科技有限公司 | 用于单细胞中的基因组dna和基因表达分析的组合物和方法 |
| CN110568039B (zh) * | 2019-09-06 | 2021-05-04 | 中国科学院生物物理研究所 | 使用新型电化学传感器的氨基酸特异实时检测方法 |
| WO2021194640A1 (en) * | 2020-03-26 | 2021-09-30 | Agilent Technologies, Inc. | Methods and compositions for multistage primer extension reactions |
| GB2605404A (en) * | 2021-03-30 | 2022-10-05 | Sumitomo Chemical Co | Sequencing method |
| WO2022263489A1 (en) * | 2021-06-17 | 2022-12-22 | F. Hoffmann-La Roche Ag | Nucleoside-5 -oligophosphates having a cationically-modified nucleobase |
| IL309368A (en) * | 2021-06-29 | 2024-02-01 | Agilent Technologies Inc | polymerase mutants and use with 3'-OH UNBLOCKED REVERSIBLE TERMINATORS |
| CN114250283B (zh) * | 2021-10-15 | 2022-10-04 | 深圳铭毅智造科技有限公司 | 基于环境敏感染料的单色荧光mrt基因测序试剂及方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0490281A1 (de) * | 1990-12-11 | 1992-06-17 | Hoechst Aktiengesellschaft | 3'- Amino- oder thiolmodifizierte, Fluoreszenzfarbstoff-gekoppelte Nukleoside, Nukleotide und Oligonukleotide sowie ein Verfahren zur Herstellung und ihre Verwendung |
| US5302509A (en) * | 1989-08-14 | 1994-04-12 | Beckman Instruments, Inc. | Method for sequencing polynucleotides |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6211165B1 (en) * | 1997-05-09 | 2001-04-03 | The Trustees Of The University Of Pennsylvania | Methods and compositions for reducing ischemic injury of the heart by administering adenosine receptor agonists and antagonists |
| US6586413B2 (en) * | 1999-11-05 | 2003-07-01 | The United States Of America As Represented By The Department Of Health And Human Services | Methods and compositions for reducing ischemic injury of the heart by administering adenosine receptor agonists and antagonists |
| AU2001296645A1 (en) | 2000-10-06 | 2002-04-15 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding dna and rna |
| DE60212642T2 (de) * | 2001-04-10 | 2007-06-14 | ECOLE POLYTECHNIQUE FéDéRALE DE LAUSANNE | Verfahren zur verwendung von o6-alkylguanin-dna-alkyltransferasen |
| GB0128526D0 (en) * | 2001-11-29 | 2002-01-23 | Amersham Pharm Biotech Uk Ltd | Nucleotide analogues |
| US7057026B2 (en) * | 2001-12-04 | 2006-06-06 | Solexa Limited | Labelled nucleotides |
| PT3438116T (pt) | 2002-08-23 | 2021-03-23 | Illumina Cambridge Ltd | Nucleótidos identificados |
| CZ294538B6 (cs) * | 2002-12-30 | 2005-01-12 | Ústav Experimentální Botaniky Akademie Vědčeské Re | Substituční deriváty N6-benzyladenosinu, způsob jejich přípravy, jejich použití pro přípravu léčiv, kosmetických přípravků a růstových regulátorů, farmaceutické přípravky, kosmetické přípravky a růstové regulátory tyto sloučeniny obsahující |
| EP2436778A3 (en) * | 2004-03-03 | 2012-07-11 | The Trustees of Columbia University in the City of New York | Photocleavable fluorescent nucleotides for DNA sequencing on chip constructed by site-specific coupling chemistry |
-
2007
- 2007-12-05 KR KR1020097013028A patent/KR101504640B1/ko active Active
- 2007-12-05 NZ NZ577303A patent/NZ577303A/en not_active IP Right Cessation
- 2007-12-05 EP EP07854973.0A patent/EP2125856B1/en active Active
- 2007-12-05 RU RU2009121089/04A patent/RU2009121089A/ru not_active Application Discontinuation
- 2007-12-05 CA CA2670937A patent/CA2670937C/en active Active
- 2007-12-05 MX MX2011013323A patent/MX338089B/es unknown
- 2007-12-05 MX MX2009005936A patent/MX2009005936A/es active IP Right Grant
- 2007-12-05 JP JP2009540462A patent/JP5513122B2/ja active Active
- 2007-12-05 AU AU2007329361A patent/AU2007329361B2/en active Active
- 2007-12-05 CN CN201110376726.1A patent/CN102443030B/zh active Active
- 2007-12-05 WO PCT/US2007/086559 patent/WO2008070749A2/en not_active Ceased
- 2007-12-05 BR BRPI0719923-6A patent/BRPI0719923B1/pt active IP Right Grant
-
2009
- 2009-06-01 IL IL199051A patent/IL199051A/en active IP Right Grant
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5302509A (en) * | 1989-08-14 | 1994-04-12 | Beckman Instruments, Inc. | Method for sequencing polynucleotides |
| EP0490281A1 (de) * | 1990-12-11 | 1992-06-17 | Hoechst Aktiengesellschaft | 3'- Amino- oder thiolmodifizierte, Fluoreszenzfarbstoff-gekoppelte Nukleoside, Nukleotide und Oligonukleotide sowie ein Verfahren zur Herstellung und ihre Verwendung |
Non-Patent Citations (2)
| Title |
|---|
| Emerging technologies in DNA sequencing;Michael L. Metzker;《Genome Res.》;20051231;第15卷;第1767-1776页 * |
| Structure-activity relationships and conformational features of antiherpetic pyrimidine and purine nucleoside analogues. A review;T. Kulikowski;《Pharmacy World and Science》;19941231;第16卷(第2期);第127-138页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| IL199051A (en) | 2013-11-28 |
| AU2007329361A1 (en) | 2008-06-12 |
| JP5513122B2 (ja) | 2014-06-04 |
| CA2670937C (en) | 2016-07-26 |
| RU2009121089A (ru) | 2011-01-20 |
| MX338089B (es) | 2016-04-01 |
| CN102443030A (zh) | 2012-05-09 |
| BRPI0719923A2 (pt) | 2014-03-04 |
| EP2125856A2 (en) | 2009-12-02 |
| AU2007329361B2 (en) | 2013-07-18 |
| CA2670937A1 (en) | 2008-06-12 |
| KR101504640B1 (ko) | 2015-03-20 |
| BRPI0719923B1 (pt) | 2021-08-17 |
| MX2009005936A (es) | 2010-01-15 |
| WO2008070749A2 (en) | 2008-06-12 |
| JP2011506265A (ja) | 2011-03-03 |
| HK1169413A1 (zh) | 2013-01-25 |
| EP2125856B1 (en) | 2016-09-14 |
| NZ577303A (en) | 2011-12-22 |
| WO2008070749A3 (en) | 2008-11-27 |
| KR20090101451A (ko) | 2009-09-28 |
| EP2125856A4 (en) | 2013-12-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102443030B (zh) | 光可断裂的标记核苷酸和核苷与标记的核苷酸和核苷以及其在dna测序中的使用方法 | |
| CN101636406A (zh) | 光可断裂的标记核苷酸和核苷与标记的核苷酸和核苷以及其在dna测序中的使用方法 | |
| JP5143953B2 (ja) | ヌクレオチドおよびヌクレオシドならびにdna配列決定におけるその使用の方法 | |
| EP3902814B1 (en) | Nucleosides and nucleotides with 3'-hydroxy blocking groups and their use in polynucleotide sequencing methods | |
| JP6196972B2 (ja) | 5−メトキシ3’−oh非遮断高速光開裂性末端ヌクレオチドおよび核酸配列決定のための方法 | |
| JP5781589B2 (ja) | 光開裂性標識ヌクレオチドとヌクレオシドおよび標識ヌクレオチドとヌクレオシドならびにdna配列決定におけるそれらの使用法 | |
| RU2818762C2 (ru) | Нуклеозиды и нуклеотиды с 3’-гидрокси блокирующими группами и их применение в способах секвенирования полинуклеотидов | |
| HK1169413B (en) | Photocleavable labeled nucleotides and nucleosides and labeled nucleotides and nucleosides and methods for their use in dna sequencing | |
| HK1163184B (en) | Nucleotides and nucleosides and methods for their use in dna sequencing | |
| HK1195076B (en) | Nucleotides and nucleosides and methods for their use in dna sequencing | |
| HK1195076A (en) | Nucleotides and nucleosides and methods for their use in dna sequencing | |
| HK1200838B (en) | 5-methoxy. 3'-oh unblocked, fast photocleavable terminating nucleotides and methods for nucleic acid sequencing | |
| NZ622268B2 (en) | 5-methoxy, 3'-oh unblocked, fast photocleavable terminating nucleotides and methods for nucleic acid sequencing |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1169413 Country of ref document: HK |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: GR Ref document number: 1169413 Country of ref document: HK |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20190430 Address after: American California Patentee after: Anjelen Sci. & Tech. Inc. Address before: American Texas Patentee before: Lasergen Inc. |