CA3082429A1 - Nucleotide derivatives containing amine masked moieties and their use in a templated and non-templated enzymatic nucleic acid synthesis - Google Patents
Nucleotide derivatives containing amine masked moieties and their use in a templated and non-templated enzymatic nucleic acid synthesis Download PDFInfo
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- CA3082429A1 CA3082429A1 CA3082429A CA3082429A CA3082429A1 CA 3082429 A1 CA3082429 A1 CA 3082429A1 CA 3082429 A CA3082429 A CA 3082429A CA 3082429 A CA3082429 A CA 3082429A CA 3082429 A1 CA3082429 A1 CA 3082429A1
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- 230000002255 enzymatic effect Effects 0.000 title claims abstract description 55
- 238000001668 nucleic acid synthesis Methods 0.000 title claims abstract description 36
- 150000001412 amines Chemical class 0.000 title claims abstract description 30
- 125000003729 nucleotide group Chemical group 0.000 title description 26
- 238000000034 method Methods 0.000 claims abstract description 75
- -1 nucleotide triphosphates Chemical class 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 114
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 43
- 230000009615 deamination Effects 0.000 claims description 42
- 238000006481 deamination reaction Methods 0.000 claims description 42
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 41
- 125000003277 amino group Chemical group 0.000 claims description 28
- 229940104302 cytosine Drugs 0.000 claims description 22
- 229930024421 Adenine Natural products 0.000 claims description 21
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 21
- 229960000643 adenine Drugs 0.000 claims description 21
- 239000000126 substance Substances 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 18
- 150000001540 azides Chemical group 0.000 claims description 17
- 230000000295 complement effect Effects 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 239000003638 chemical reducing agent Substances 0.000 claims description 12
- 230000000873 masking effect Effects 0.000 claims description 12
- 125000002264 triphosphate group Chemical group [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 claims description 11
- 229910019142 PO4 Inorganic materials 0.000 claims description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 10
- 239000010452 phosphate Substances 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 10
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 8
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 8
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 8
- 125000003047 N-acetyl group Chemical group 0.000 claims description 8
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 8
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 8
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 8
- 230000005670 electromagnetic radiation Effects 0.000 claims description 6
- DRAVOWXCEBXPTN-UHFFFAOYSA-N isoguanine Chemical compound NC1=NC(=O)NC2=C1NC=N2 DRAVOWXCEBXPTN-UHFFFAOYSA-N 0.000 claims description 6
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 4
- NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 claims description 4
- ZZOKVYOCRSMTSS-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl carbamate Chemical compound C1=CC=C2C(COC(=O)N)C3=CC=CC=C3C2=C1 ZZOKVYOCRSMTSS-UHFFFAOYSA-N 0.000 claims description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
- PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 claims description 4
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims description 4
- 150000002540 isothiocyanates Chemical class 0.000 claims description 4
- XDIIJQFNVMXIJQ-UHFFFAOYSA-N n-methylacetohydrazide Chemical compound CN(N)C(C)=O XDIIJQFNVMXIJQ-UHFFFAOYSA-N 0.000 claims description 4
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 4
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 claims description 4
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 claims description 4
- BZVJOYBTLHNRDW-UHFFFAOYSA-N triphenylmethanamine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(N)C1=CC=CC=C1 BZVJOYBTLHNRDW-UHFFFAOYSA-N 0.000 claims description 4
- XQCZBXHVTFVIFE-UHFFFAOYSA-N 2-amino-4-hydroxypyrimidine Chemical compound NC1=NC=CC(O)=N1 XQCZBXHVTFVIFE-UHFFFAOYSA-N 0.000 claims description 3
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 claims description 3
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 150000003973 alkyl amines Chemical class 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 229960002685 biotin Drugs 0.000 claims description 2
- 235000020958 biotin Nutrition 0.000 claims description 2
- 239000011616 biotin Substances 0.000 claims description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 claims description 2
- 230000002068 genetic effect Effects 0.000 claims description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical group OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 claims description 2
- YICAEXQYKBMDNH-UHFFFAOYSA-N 3-[bis(3-hydroxypropyl)phosphanyl]propan-1-ol Chemical compound OCCCP(CCCO)CCCO YICAEXQYKBMDNH-UHFFFAOYSA-N 0.000 claims 2
- JMXMXKRNIYCNRV-UHFFFAOYSA-N bis(hydroxymethyl)phosphanylmethanol Chemical compound OCP(CO)CO JMXMXKRNIYCNRV-UHFFFAOYSA-N 0.000 claims 2
- 239000001226 triphosphate Substances 0.000 abstract description 38
- 239000002773 nucleotide Substances 0.000 abstract description 26
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 235000011178 triphosphate Nutrition 0.000 abstract description 3
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 62
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 108020004414 DNA Proteins 0.000 description 32
- 235000010288 sodium nitrite Nutrition 0.000 description 31
- 230000006820 DNA synthesis Effects 0.000 description 27
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 22
- 239000005695 Ammonium acetate Substances 0.000 description 22
- 235000019257 ammonium acetate Nutrition 0.000 description 22
- 229940043376 ammonium acetate Drugs 0.000 description 22
- 102000053602 DNA Human genes 0.000 description 20
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 18
- 238000007833 oxidative deamination reaction Methods 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 17
- 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 16
- 238000006243 chemical reaction Methods 0.000 description 14
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 13
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 11
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 10
- 239000001632 sodium acetate Substances 0.000 description 10
- 235000017281 sodium acetate Nutrition 0.000 description 10
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 230000002378 acidificating effect Effects 0.000 description 9
- VGONTNSXDCQUGY-UHFFFAOYSA-N desoxyinosine Natural products C1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 VGONTNSXDCQUGY-UHFFFAOYSA-N 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- 102000039446 nucleic acids Human genes 0.000 description 8
- 108020004707 nucleic acids Proteins 0.000 description 8
- 230000002441 reversible effect Effects 0.000 description 8
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- 230000000694 effects Effects 0.000 description 7
- CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 description 6
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
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- 150000007523 nucleic acids Chemical class 0.000 description 6
- 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 5
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- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
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- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
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- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
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- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
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- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
- C12P19/28—N-glycosides
- C12P19/30—Nucleotides
- C12P19/34—Polynucleotides, e.g. nucleic acids, oligoribonucleotides
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- C12Y—ENZYMES
- C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
- C12Y207/07—Nucleotidyltransferases (2.7.7)
- C12Y207/07031—DNA nucleotidylexotransferase (2.7.7.31), i.e. terminal deoxynucleotidyl transferase
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6844—Nucleic acid amplification reactions
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- C12Q2525/00—Reactions involving modified oligonucleotides, nucleic acids, or nucleotides
- C12Q2525/10—Modifications characterised by
- C12Q2525/117—Modifications characterised by incorporating modified base
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1718804.6A GB201718804D0 (en) | 2017-11-14 | 2017-11-14 | Novel use |
| GB1718804.6 | 2017-11-14 | ||
| PCT/GB2018/053305 WO2019097233A1 (en) | 2017-11-14 | 2018-11-14 | Nucleotide derivatives containing amine masked moieties and their use in a templated and non-templated enzymatic nucleic acid synthesis |
Publications (1)
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| CA3082429A1 true CA3082429A1 (en) | 2019-05-23 |
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Family Applications (1)
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| CA3082429A Pending CA3082429A1 (en) | 2017-11-14 | 2018-11-14 | Nucleotide derivatives containing amine masked moieties and their use in a templated and non-templated enzymatic nucleic acid synthesis |
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| JP (1) | JP2021503003A (https=) |
| CN (1) | CN111344296A (https=) |
| AU (1) | AU2018366391A1 (https=) |
| CA (1) | CA3082429A1 (https=) |
| GB (2) | GB201718804D0 (https=) |
| WO (1) | WO2019097233A1 (https=) |
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| AU2019311199B2 (en) | 2018-07-23 | 2024-12-19 | Dna Script | Massively parallel enzymatic synthesis of nucleic acid strands |
| SG11202105441WA (en) | 2018-12-13 | 2021-06-29 | Dna Script | Direct oligonucleotide synthesis on cells and biomolecules |
| SG11202107921SA (en) | 2019-02-12 | 2021-08-30 | Dna Script | Efficient product cleavage in template-free enzymatic synthesis of polynucleotides. |
| WO2020165334A1 (en) * | 2019-02-14 | 2020-08-20 | Dna Script | Process for preparing 3'-o-amino-ribonucleotide |
| GB201906772D0 (en) * | 2019-05-14 | 2019-06-26 | Nuclera Nucleics Ltd | Nucleic acid polymer with amine-masked bases |
| EP4126895A1 (en) * | 2020-03-30 | 2023-02-08 | DNA Script | Method for preparing 3'-o-amino-2'-deoxyribonucleoside-5'-triphosphates |
| EP4132941A2 (en) * | 2020-04-06 | 2023-02-15 | Nuclera Nucleics Ltd | 3'-aminooxy-c5-substituted cytosine nucleotide derivatives and their use in a templated and non-templated enzymatic nucleic acid synthesis |
| GB202005043D0 (en) * | 2020-04-06 | 2020-05-20 | Nuclera Nucleics Ltd | C5-modified Thymidines |
| US11850258B1 (en) * | 2020-05-29 | 2023-12-26 | Nilesh B. Karalkar | Ribonucleoside derivatives with 3′-aminoxy groups |
| WO2024227846A2 (en) | 2023-05-03 | 2024-11-07 | Dna Script | Reagent used in deprotection of 3'-o-amino polynucleotides |
| CN116949152B (zh) * | 2023-06-16 | 2025-03-11 | 广州国家实验室 | 一种单碱基水平检测基因组DNA上N4-mC及5mC修饰的测序方法 |
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| JP3022967B2 (ja) * | 1985-03-15 | 2000-03-21 | アンチバイラルズ インコーポレイテッド | 立体規則性ポリヌクレオチド結合ポリマー |
| US4672111A (en) * | 1985-04-23 | 1987-06-09 | University Of Wyoming | 5-azido-deoxyuridine compounds and method of synthesis of the same |
| DE3739366A1 (de) * | 1987-04-10 | 1988-10-27 | Boehringer Mannheim Gmbh | Desaza-purin-nucleosid-derivate, verfahren zu deren herstellung sowie deren verwendung bei der nucleinsaeure-sequenzierung sowie als antivirale mittel |
| JPH11512397A (ja) * | 1995-09-07 | 1999-10-26 | ユニバーシティー オブ ジョージア リサーチ ファウンデーション，インコーポレイテッド | 治療用アジド化合物 |
| IT1377936B1 (it) | 2007-03-28 | 2010-07-30 | Nucleotidi piridinici acitali, loro reparazione ed uso | |
| JP2011520845A (ja) * | 2008-05-15 | 2011-07-21 | カソリック ユニヴェルシテイト ルーヴェン，ケー．ユー． ルーヴェン アール アンド ディー | 抗癌剤の組合せによる治療 |
| US8034923B1 (en) * | 2009-03-27 | 2011-10-11 | Steven Albert Benner | Reagents for reversibly terminating primer extension |
| US9309569B2 (en) * | 2010-08-26 | 2016-04-12 | Intelligent Bio-Systems, Inc. | Methods and compositions for sequencing nucleic acid using charge |
| KR101794970B1 (ko) * | 2010-11-12 | 2017-11-07 | (주)비씨월드제약 | 신규한 뉴클레오시드 유도체 |
| KR101093787B1 (ko) * | 2011-06-10 | 2011-12-19 | (주)비씨월드제약 | 신규한 뉴클레오시드 유도체를 포함하는 암 치료용 약학적 조성물 |
| GB201502152D0 (en) * | 2015-02-10 | 2015-03-25 | Nuclera Nucleics Ltd | Novel use |
| WO2017087887A1 (en) * | 2015-11-18 | 2017-05-26 | The Trustees Of Columbia University In The City Of New York | Ion sensor dna and rna sequencing by synthesis using nucleotide reversible terminators |
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2017
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2018
- 2018-11-14 CN CN201880073408.8A patent/CN111344296A/zh active Pending
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- 2018-11-14 GB GB1818605.6A patent/GB2568397A/en not_active Withdrawn
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| EP3710461A1 (en) | 2020-09-23 |
| WO2019097233A1 (en) | 2019-05-23 |
| GB201818605D0 (en) | 2018-12-26 |
| AU2018366391A1 (en) | 2020-06-25 |
| GB201718804D0 (en) | 2017-12-27 |
| GB2568397A (en) | 2019-05-15 |
| US11505815B2 (en) | 2022-11-22 |
| US20190144905A1 (en) | 2019-05-16 |
| JP2021503003A (ja) | 2021-02-04 |
| CN111344296A (zh) | 2020-06-26 |
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