CA1200771A - Supports utilises dans la synthese de polynucleotides et procede de production et d'utilisation - Google Patents

Supports utilises dans la synthese de polynucleotides et procede de production et d'utilisation

Info

Publication number: CA1200771A
Authority: CA; Canada
Prior art keywords: nucleoside; polymer; group; process according; support
Prior art date: 1980-02-29
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

Application number

CA000449718A

Other languages

English (en)

Inventor

Marvin H. Caruthers

Mark D. Matteucci

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

University Patents Inc

Original Assignee

University Patents Inc

Priority date (The priority date 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 date listed.)

1980-02-29

Filing date

1984-03-15

Publication date

1986-02-18

1981-02-27 Priority claimed from CA000371946A external-priority patent/CA1168229A/fr

1984-03-15 Application filed by University Patents Inc filed Critical University Patents Inc

1984-03-15 Priority to CA000449718A priority Critical patent/CA1200771A/fr

1985-04-11 Priority to CA000478943A priority patent/CA1203968A/fr

1986-02-18 Application granted granted Critical

1986-02-18 Publication of CA1200771A publication Critical patent/CA1200771A/fr

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 89
230000008569 process Effects 0.000 title claims abstract description 58
230000015572 biosynthetic process Effects 0.000 title abstract description 24
238000003786 synthesis reaction Methods 0.000 title abstract description 19
108091033319 polynucleotide Proteins 0.000 title description 11
239000002157 polynucleotide Substances 0.000 title description 11
102000040430 polynucleotide Human genes 0.000 title description 11
239000002777 nucleoside Substances 0.000 claims abstract description 159
150000003833 nucleoside derivatives Chemical class 0.000 claims abstract description 129
-1 phosphite compound Chemical class 0.000 claims abstract description 63
108091034117 Oligonucleotide Proteins 0.000 claims abstract description 61
230000000903 blocking effect Effects 0.000 claims abstract description 48
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 claims abstract description 31
125000003835 nucleoside group Chemical group 0.000 claims abstract description 24
229920000592 inorganic polymer Polymers 0.000 claims abstract description 22
238000004519 manufacturing process Methods 0.000 claims abstract description 21
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims abstract description 13
239000007822 coupling agent Substances 0.000 claims abstract description 10
125000000217 alkyl group Chemical group 0.000 claims abstract description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 158
239000000741 silica gel Substances 0.000 claims description 80
229910002027 silica gel Inorganic materials 0.000 claims description 80
229920000642 polymer Polymers 0.000 claims description 67
125000003729 nucleotide group Chemical group 0.000 claims description 44
238000006243 chemical reaction Methods 0.000 claims description 42
VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 claims description 41
239000002773 nucleotide Substances 0.000 claims description 35
239000000377 silicon dioxide Substances 0.000 claims description 30
150000001875 compounds Chemical class 0.000 claims description 24
238000005859 coupling reaction Methods 0.000 claims description 22
OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 claims description 21
230000008878 coupling Effects 0.000 claims description 20
238000010168 coupling process Methods 0.000 claims description 20
150000002148 esters Chemical class 0.000 claims description 20
238000009833 condensation Methods 0.000 claims description 16
230000005494 condensation Effects 0.000 claims description 16
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 12
239000002841 Lewis acid Substances 0.000 claims description 10
229910019142 PO4 Inorganic materials 0.000 claims description 10
OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical group NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 10
150000007517 lewis acids Chemical class 0.000 claims description 10
239000010452 phosphate Substances 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 9
239000000126 substance Substances 0.000 claims description 9
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical group C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 8
125000004432 carbon atom Chemical group C* 0.000 claims description 8
UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical group O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 8
229940104302 cytosine Drugs 0.000 claims description 5
239000007800 oxidant agent Substances 0.000 claims description 5
RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical group CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 4
229940102001 zinc bromide Drugs 0.000 claims description 4
239000002126 C01EB10 - Adenosine Chemical group 0.000 claims description 3
229960005305 adenosine Drugs 0.000 claims description 3
238000006482 condensation reaction Methods 0.000 claims description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
125000001424 substituent group Chemical group 0.000 claims description 3
125000002947 alkylene group Chemical group 0.000 claims description 2
239000003795 chemical substances by application Substances 0.000 claims description 2
125000003831 tetrazolyl group Chemical group 0.000 claims description 2
229940113082 thymine Drugs 0.000 claims description 2
230000001590 oxidative effect Effects 0.000 claims 2
125000001425 triazolyl group Chemical group 0.000 claims 1
229920001184 polypeptide Polymers 0.000 abstract 1
102000004196 processed proteins & peptides Human genes 0.000 abstract 1
108090000765 processed proteins & peptides Proteins 0.000 abstract 1
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 63
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
239000000243 solution Substances 0.000 description 38
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 36
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
239000002904 solvent Substances 0.000 description 26
238000007792 addition Methods 0.000 description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
239000002253 acid Substances 0.000 description 20
239000000047 product Substances 0.000 description 20
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical class CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 18
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 18
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
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 17
239000003153 chemical reaction reagent Substances 0.000 description 15
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
238000006642 detritylation reaction Methods 0.000 description 12
238000005406 washing Methods 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
150000007513 acids Chemical class 0.000 description 9
150000001732 carboxylic acid derivatives Chemical class 0.000 description 9
230000003647 oxidation Effects 0.000 description 9
238000007254 oxidation reaction Methods 0.000 description 9
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
125000003277 amino group Chemical group 0.000 description 8
238000004458 analytical method Methods 0.000 description 8
238000005119 centrifugation Methods 0.000 description 8
239000011159 matrix material Substances 0.000 description 8
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 8
BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 7
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 7
238000005755 formation reaction Methods 0.000 description 7
238000010992 reflux Methods 0.000 description 7
238000000926 separation method Methods 0.000 description 7
239000006228 supernatant Substances 0.000 description 7
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
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 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
229910052786 argon Inorganic materials 0.000 description 6
IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
230000000875 corresponding effect Effects 0.000 description 6
239000000203 mixture Substances 0.000 description 6
229940014800 succinic anhydride Drugs 0.000 description 6
239000000725 suspension Substances 0.000 description 6
229940104230 thymidine Drugs 0.000 description 6
150000005691 triesters Chemical class 0.000 description 6
WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical compound CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 description 5
UBTJZUKVKGZHAD-UHFFFAOYSA-N 1-[5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)(C=1C=CC=CC=1)OCC1C(O)CC(N2C(NC(=O)C(C)=C2)=O)O1 UBTJZUKVKGZHAD-UHFFFAOYSA-N 0.000 description 5
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150000001412 amines Chemical class 0.000 description 5
239000000908 ammonium hydroxide Substances 0.000 description 5
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238000003776 cleavage reaction Methods 0.000 description 5
230000027832 depurination Effects 0.000 description 5
239000000499 gel Substances 0.000 description 5
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 5
238000011068 loading method Methods 0.000 description 5
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
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150000003536 tetrazoles Chemical class 0.000 description 5
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230000010933 acylation Effects 0.000 description 4
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HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 4
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IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
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HCSDJECSMANTCX-UHFFFAOYSA-N dichloro(methoxy)phosphane Chemical compound COP(Cl)Cl HCSDJECSMANTCX-UHFFFAOYSA-N 0.000 description 4
238000001035 drying Methods 0.000 description 4
238000000605 extraction Methods 0.000 description 4
239000011521 glass Substances 0.000 description 4
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical class [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
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238000011010 flushing procedure Methods 0.000 description 3
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238000006460 hydrolysis reaction Methods 0.000 description 3
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VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
125000004888 n-propyl amino group Chemical group [H]N(*)C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
238000001556 precipitation Methods 0.000 description 3
239000000376 reactant Substances 0.000 description 3
230000002441 reversible effect Effects 0.000 description 3
229920002477 rna polymer Polymers 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
238000010561 standard procedure Methods 0.000 description 3
230000002194 synthesizing effect Effects 0.000 description 3
238000012360 testing method Methods 0.000 description 3
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
239000002699 waste material Substances 0.000 description 3
YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 description 2
LKPFWCPZERQLFI-UHFFFAOYSA-N 2,4,6-trimethylpyridine;hydrochloride Chemical compound Cl.CC1=CC(C)=NC(C)=C1 LKPFWCPZERQLFI-UHFFFAOYSA-N 0.000 description 2
YZEUHQHUFTYLPH-UHFFFAOYSA-N 2-nitroimidazole Chemical compound [O-][N+](=O)C1=NC=CN1 YZEUHQHUFTYLPH-UHFFFAOYSA-N 0.000 description 2
JDQDSEVNMTYMOC-UHFFFAOYSA-N 3-methylbenzenesulfonic acid Chemical compound CC1=CC=CC(S(O)(=O)=O)=C1 JDQDSEVNMTYMOC-UHFFFAOYSA-N 0.000 description 2
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229910000077 silane Inorganic materials 0.000 description 1
SCPYDCQAZCOKTP-UHFFFAOYSA-N silanol Chemical compound [SiH3]O SCPYDCQAZCOKTP-UHFFFAOYSA-N 0.000 description 1
125000005372 silanol group Chemical group 0.000 description 1
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
238000006884 silylation reaction Methods 0.000 description 1
239000003998 snake venom Substances 0.000 description 1
108010062513 snake venom phosphodiesterase I Proteins 0.000 description 1
239000007787 solid Substances 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
241000894007 species Species 0.000 description 1
238000002798 spectrophotometry method Methods 0.000 description 1
238000003860 storage Methods 0.000 description 1
229920002994 synthetic fiber Polymers 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
239000010936 titanium Substances 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
238000012546 transfer Methods 0.000 description 1
125000005369 trialkoxysilyl group Chemical group 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
239000005051 trimethylchlorosilane Substances 0.000 description 1
239000003643 water by type Substances 0.000 description 1
239000011701 zinc Substances 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1

Classifications

- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials

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Saccharide Compounds (AREA)

CA000449718A 1980-02-29 1984-03-15 Supports utilises dans la synthese de polynucleotides et procede de production et d'utilisation Expired CA1200771A (fr)

Priority Applications (2)

Application Number	Priority Date	Filing Date	Title
CA000449718A CA1200771A (fr)	1980-02-29	1984-03-15	Supports utilises dans la synthese de polynucleotides et procede de production et d'utilisation
CA000478943A CA1203968A (fr)	1980-02-29	1985-04-11	Supports utilises pour la synthese des polynucleotides et appareil utilise pour leur fabrication

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US12602580A	1980-02-29	1980-02-29
US126,025		1980-02-29
CA000371946A CA1168229A (fr)	1980-02-29	1981-02-27	Moyens utilises pour la synthese de polynucleotides; methode de preparation et applications
CA000449718A CA1200771A (fr)	1980-02-29	1984-03-15	Supports utilises dans la synthese de polynucleotides et procede de production et d'utilisation

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000371946A Division CA1168229A (fr)	1980-02-29	1981-02-27	Moyens utilises pour la synthese de polynucleotides; methode de preparation et applications

Related Child Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000478943A Division CA1203968A (fr)	1980-02-29	1985-04-11	Supports utilises pour la synthese des polynucleotides et appareil utilise pour leur fabrication

Publications (1)

Publication Number	Publication Date
CA1200771A true CA1200771A (fr)	1986-02-18

Family

ID=25669266

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000449718A Expired CA1200771A (fr)	1980-02-29	1984-03-15	Supports utilises dans la synthese de polynucleotides et procede de production et d'utilisation

Country Status (1)

Country	Link
CA (1)	CA1200771A (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN112919480A (zh) *	2021-02-01	2021-06-08	中国石油天然气股份有限公司	双羟基硅胶及其制备方法、采出液中功能型聚合物浓度的检测系统

1984
- 1984-03-15 CA CA000449718A patent/CA1200771A/fr not_active Expired

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN112919480A (zh) *	2021-02-01	2021-06-08	中国石油天然气股份有限公司	双羟基硅胶及其制备方法、采出液中功能型聚合物浓度的检测系统

Legal Events

Date	Code	Title	Description
2003-02-18	MKEX	Expiry

Publication	Publication Date	Title
CA1168229A (fr)	1984-05-29	Moyens utilises pour la synthese de polynucleotides; methode de preparation et applications
US4458066A (en)	1984-07-03	Process for preparing polynucleotides
US5153319A (en)	1992-10-06	Process for preparing polynucleotides
US5132418A (en)	1992-07-21	Process for preparing polynucleotides
US4500707A (en)	1985-02-19	Nucleosides useful in the preparation of polynucleotides
Caruthers et al.	1987	[15] Chemical synthesis of deoxyoligonucleotides by the phosphoramidite method
US5700919A (en)	1997-12-23	Modified phosphoramidite process for the production of modified nucleic acids
EP0794001B1 (fr)	2000-10-11	Système automatique pour la synthèse et purification de polynucléotides
EP0101985B1 (fr)	1987-09-23	Dérivés d'oligonucléotides et leur procédé de préparation
Matteucci et al.	1981	Synthesis of deoxyoligonucleotides on a polymer support
EP0061746B1 (fr)	1985-03-20	Dérivés de phosphoramidite et leur emploi dans la fabrication d'oligonucléotides
US4659774A (en)	1987-04-21	Support for solid-phase oligonucleotide synthesis
US6262251B1 (en)	2001-07-17	Method for solution phase synthesis of oligonucleotides
AU737213B2 (en)	2001-08-09	Method for solution phase synthesis of oligonucleotides and peptides
CA1220747A (fr)	1987-04-21	Appareil de synthese de composes chimiques
WO1992002535A1 (fr)	1992-02-20	Systeme automatique de synthese et de purification de polynucleotides
US6001966A (en)	1999-12-14	Method for solution phase synthesis of oligonucleotides and peptides
EP0398391B1 (fr)	1995-08-16	0,0'-Dicyanoéthyl-phosphoramidites, un procédé pour leur préparation et leur utilisation dans des réactions de phosphorylation
CA1200771A (fr)	1986-02-18	Supports utilises dans la synthese de polynucleotides et procede de production et d'utilisation
CA1203968A (fr)	1986-05-06	Supports utilises pour la synthese des polynucleotides et appareil utilise pour leur fabrication
Caruthers	1987	DNA synthesis for nonchemists: the phosphoramidite method on silica supports
Caruthers	1987	Modern methods of nucleic acid synthesis on polymeric supports

CA1200771A - Supports utilises dans la synthese de polynucleotides et procede de production et d'utilisation - Google Patents

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Links

Classifications

Landscapes

Priority Applications (2)

Applications Claiming Priority (4)

Related Parent Applications (1)

Related Child Applications (1)

Publications (1)

Family

ID=25669266

Family Applications (1)

Country Status (1)

Cited By (1)

Cited By (1)

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