CA2361079C - Method for deprotecting oligonucleotides - Google Patents
Method for deprotecting oligonucleotides Download PDFInfo
- Publication number
- CA2361079C CA2361079C CA2361079A CA2361079A CA2361079C CA 2361079 C CA2361079 C CA 2361079C CA 2361079 A CA2361079 A CA 2361079A CA 2361079 A CA2361079 A CA 2361079A CA 2361079 C CA2361079 C CA 2361079C
- Authority
- CA
- Canada
- Prior art keywords
- oligonucleotide
- substrate
- phosphate protecting
- reagent
- protecting groups
- 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 - Fee Related
Links
- 108091034117 Oligonucleotide Proteins 0.000 title claims abstract description 150
- 238000000034 method Methods 0.000 title claims abstract description 40
- 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 title description 39
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
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- 239000011368 organic material Substances 0.000 claims description 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims 1
- 150000004713 phosphodiesters Chemical class 0.000 claims 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims 1
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- 239000012535 impurity Substances 0.000 description 18
- 238000010511 deprotection reaction Methods 0.000 description 16
- 239000002777 nucleoside Substances 0.000 description 14
- -1 Phosphate triester Chemical class 0.000 description 13
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- 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 8
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- 229910019142 PO4 Inorganic materials 0.000 description 6
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- 238000012360 testing method Methods 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 150000003538 tetroses Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- 150000003641 trioses Chemical class 0.000 description 1
- 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 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005406 washing Methods 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
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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)
- Saccharide Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11857599P | 1999-02-05 | 1999-02-05 | |
| US60/118,575 | 1999-02-05 | ||
| PCT/US2000/002845 WO2000046231A1 (en) | 1999-02-05 | 2000-02-05 | Method for deprotecting oligonucleotides |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2361079A1 CA2361079A1 (en) | 2000-08-10 |
| CA2361079C true CA2361079C (en) | 2010-05-25 |
Family
ID=22379444
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2361079A Expired - Fee Related CA2361079C (en) | 1999-02-05 | 2000-02-05 | Method for deprotecting oligonucleotides |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US6887990B1 (https=) |
| EP (1) | EP1149109B1 (https=) |
| JP (1) | JP4705716B2 (https=) |
| AT (1) | ATE443071T1 (https=) |
| AU (1) | AU767509B2 (https=) |
| CA (1) | CA2361079C (https=) |
| DE (1) | DE60042962D1 (https=) |
| DK (1) | DK1149109T3 (https=) |
| NO (1) | NO20013804L (https=) |
| WO (1) | WO2000046231A1 (https=) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4503828B2 (ja) | 1998-02-11 | 2010-07-14 | ユニバーシティー オブ ヒューストン | 光生成試薬を用いる化学反応および生化学反応のための方法および装置 |
| US6465628B1 (en) | 1999-02-04 | 2002-10-15 | Isis Pharmaceuticals, Inc. | Process for the synthesis of oligomeric compounds |
| WO2002046205A2 (en) | 2000-12-05 | 2002-06-13 | Avecia Limited | Process for the preparation of phosphorothionate oligonucleotides |
| US6768005B2 (en) | 2000-12-20 | 2004-07-27 | Avecia Limited | Process |
| JP2004521628A (ja) | 2001-03-08 | 2004-07-22 | アプレラ コーポレイション | オリゴヌクレオチドの切断および脱保護のための試薬 |
| US7211654B2 (en) | 2001-03-14 | 2007-05-01 | Regents Of The University Of Michigan | Linkers and co-coupling agents for optimization of oligonucleotide synthesis and purification on solid supports |
| US20030153741A1 (en) * | 2002-02-08 | 2003-08-14 | Marek Kwiatkowski | Methods for separating oligonucleotides |
| US8138330B2 (en) * | 2006-09-11 | 2012-03-20 | Sigma-Aldrich Co. Llc | Process for the synthesis of oligonucleotides |
| US8513404B2 (en) * | 2008-04-24 | 2013-08-20 | Nitto Denko Avecia, Inc. | Process for the manufacture of oligonucleotides |
| WO2021045141A1 (ja) * | 2019-09-04 | 2021-03-11 | 神戸天然物化学株式会社 | オリゴヌクレオチドの脱保護方法 |
| US12509483B2 (en) | 2019-10-11 | 2025-12-30 | Sumitomo Chemical Company, Limited | Method for producing nucleic acid oligomers |
| WO2021153770A1 (en) | 2020-01-29 | 2021-08-05 | Sumitomo Chemical Company, Limited | Process of preparing nucleic acid oligomer |
| US20230312635A1 (en) | 2020-01-29 | 2023-10-05 | Sumitomo Chemical Company, Limited | Method for producing nucleic acid oligomer |
| US12522629B2 (en) | 2020-03-27 | 2026-01-13 | Sumitomo Chemical Company, Limited | Method for producing nucleic acid oligomer |
| US20230242570A1 (en) | 2020-07-09 | 2023-08-03 | Sumitomo Chemical Company, Limited | Method for producing nucleic acid oligomer |
| JP7719788B2 (ja) | 2020-09-24 | 2025-08-06 | 住友化学株式会社 | 核酸オリゴマーの製造方法 |
| KR20240082343A (ko) | 2021-09-28 | 2024-06-10 | 스미또모 가가꾸 가부시끼가이샤 | 정제 디클로로아세트산의 제조 방법 |
| EP4201947A1 (en) | 2021-12-22 | 2023-06-28 | F. Hoffmann-La Roche AG | Process for the backbone deprotection of oligonucleotides containing a terminal alkyl phosphonate group |
| CN114573652B (zh) * | 2022-03-15 | 2025-02-07 | 安徽瑞拜药业有限公司 | 药用核酸合成工艺 |
| KR20240162536A (ko) | 2022-03-23 | 2024-11-15 | 스미또모 가가꾸 가부시끼가이샤 | 핵산 올리고머의 제조 방법 |
| EP4559925A1 (en) | 2022-07-22 | 2025-05-28 | Sumitomo Chemical Company, Limited | Production method of oligonucleotide |
| KR20250046255A (ko) | 2022-07-28 | 2025-04-02 | 스미또모 가가꾸 가부시끼가이샤 | 티오화 용액 |
| US20250361540A1 (en) * | 2022-09-07 | 2025-11-27 | Nippon Shokubai Co., Ltd. | Nucleic acid production method, method for removing impurities, and nucleic acid having less impurities |
| JP7825064B2 (ja) | 2022-10-27 | 2026-03-05 | 住友化学株式会社 | オリゴヌクレオチドの製造方法 |
| US12415172B2 (en) | 2022-12-22 | 2025-09-16 | Synthego Corporation | Systems and method for automated oligonucleotide synthesis |
| CN120418262A (zh) | 2022-12-26 | 2025-08-01 | 住友化学株式会社 | 寡核苷酸的制造方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4426517A (en) * | 1981-08-24 | 1984-01-17 | Eli Lilly And Company | Process for de-cyanoethylating blocked nucleotides |
| US4417046A (en) * | 1981-08-24 | 1983-11-22 | Eli Lilly And Company | Process for isolating oligonucleotide product from a coupling reaction mixture |
| FR2540122B1 (fr) * | 1983-01-27 | 1985-11-29 | Centre Nat Rech Scient | Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application |
| US5362866A (en) * | 1983-09-02 | 1994-11-08 | Molecular Biosystems, Inc. | Oligonucleotide polymeric support system with an oxidation cleavable link |
| DE3481060D1 (de) * | 1983-09-02 | 1990-02-22 | Molecular Biosystems Inc | Oligonukleotid-polymer-tragsystem. |
| US4672110A (en) | 1983-11-29 | 1987-06-09 | Northwestern University | Method of deprotecting polynucleotide trimethylethyl phosphotriesters |
| JPS6242997A (ja) * | 1985-08-19 | 1987-02-24 | Akira Kaji | ヌクレオシドアルキルホスホネイトの製造方法 |
| SE9003743D0 (sv) * | 1990-11-26 | 1990-11-26 | Pharmacia Ab | Method and means for oligonucleotide synthesis |
| DE19627898A1 (de) * | 1996-07-11 | 1998-01-15 | Hoechst Ag | Festphasensynthese von Oligonucleotiden |
| US6127533A (en) * | 1997-02-14 | 2000-10-03 | Isis Pharmaceuticals, Inc. | 2'-O-aminooxy-modified oligonucleotides |
| US6465628B1 (en) * | 1999-02-04 | 2002-10-15 | Isis Pharmaceuticals, Inc. | Process for the synthesis of oligomeric compounds |
-
2000
- 2000-02-05 DK DK00907140T patent/DK1149109T3/da active
- 2000-02-05 US US09/498,773 patent/US6887990B1/en not_active Expired - Lifetime
- 2000-02-05 DE DE60042962T patent/DE60042962D1/de not_active Expired - Lifetime
- 2000-02-05 WO PCT/US2000/002845 patent/WO2000046231A1/en not_active Ceased
- 2000-02-05 AT AT00907140T patent/ATE443071T1/de not_active IP Right Cessation
- 2000-02-05 JP JP2000597301A patent/JP4705716B2/ja not_active Expired - Lifetime
- 2000-02-05 EP EP00907140A patent/EP1149109B1/en not_active Expired - Lifetime
- 2000-02-05 CA CA2361079A patent/CA2361079C/en not_active Expired - Fee Related
- 2000-02-05 AU AU28687/00A patent/AU767509B2/en not_active Ceased
-
2001
- 2001-08-03 NO NO20013804A patent/NO20013804L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO20013804L (no) | 2001-08-22 |
| DE60042962D1 (de) | 2009-10-29 |
| AU2868700A (en) | 2000-08-25 |
| DK1149109T3 (da) | 2010-01-11 |
| JP4705716B2 (ja) | 2011-06-22 |
| AU767509B2 (en) | 2003-11-13 |
| EP1149109A1 (en) | 2001-10-31 |
| WO2000046231A1 (en) | 2000-08-10 |
| CA2361079A1 (en) | 2000-08-10 |
| NO20013804D0 (no) | 2001-08-03 |
| US6887990B1 (en) | 2005-05-03 |
| JP2002536381A (ja) | 2002-10-29 |
| ATE443071T1 (de) | 2009-10-15 |
| EP1149109B1 (en) | 2009-09-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20150205 |