HRP20200250T1 - Metoda site-specifično enzimsko obilježavanje nukleinskih kiselina in vitro ugradnjom neprirodnih nukleotida - Google Patents
Metoda site-specifično enzimsko obilježavanje nukleinskih kiselina in vitro ugradnjom neprirodnih nukleotida Download PDFInfo
- Publication number
- HRP20200250T1 HRP20200250T1 HRP20200250TT HRP20200250T HRP20200250T1 HR P20200250 T1 HRP20200250 T1 HR P20200250T1 HR P20200250T T HRP20200250T T HR P20200250TT HR P20200250 T HRP20200250 T HR P20200250T HR P20200250 T1 HRP20200250 T1 HR P20200250T1
- Authority
- HR
- Croatia
- Prior art keywords
- group
- reactive
- complementary
- delivery
- nucleobase
- Prior art date
Links
- 238000010348 incorporation Methods 0.000 title claims 3
- 238000000034 method Methods 0.000 title claims 3
- 239000002773 nucleotide Substances 0.000 title claims 3
- 125000003729 nucleotide group Chemical group 0.000 title claims 3
- 230000002255 enzymatic effect Effects 0.000 title 1
- 238000000338 in vitro Methods 0.000 title 1
- 238000002372 labelling Methods 0.000 title 1
- 150000007523 nucleic acids Chemical class 0.000 title 1
- 102000039446 nucleic acids Human genes 0.000 title 1
- 108020004707 nucleic acids Proteins 0.000 title 1
- 108091034117 Oligonucleotide Proteins 0.000 claims 29
- 230000000295 complement effect Effects 0.000 claims 23
- 125000005647 linker group Chemical group 0.000 claims 18
- 150000001875 compounds Chemical class 0.000 claims 17
- 239000003153 chemical reaction reagent Substances 0.000 claims 15
- 125000000824 D-ribofuranosyl group Chemical group [H]OC([H])([H])[C@@]1([H])OC([H])(*)[C@]([H])(O[H])[C@]1([H])O[H] 0.000 claims 12
- 238000006243 chemical reaction Methods 0.000 claims 10
- 230000009257 reactivity Effects 0.000 claims 9
- 229910052739 hydrogen Inorganic materials 0.000 claims 7
- 239000001257 hydrogen Substances 0.000 claims 7
- 125000003172 aldehyde group Chemical group 0.000 claims 6
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 claims 6
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 4
- 150000002431 hydrogen Chemical group 0.000 claims 4
- 229910052717 sulfur Inorganic materials 0.000 claims 4
- 239000011593 sulfur Substances 0.000 claims 4
- 125000003396 thiol group Chemical group [H]S* 0.000 claims 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 3
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 229910052799 carbon Inorganic materials 0.000 claims 3
- 239000001177 diphosphate Substances 0.000 claims 3
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims 3
- 235000011180 diphosphates Nutrition 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- 150000004712 monophosphates Chemical class 0.000 claims 3
- 125000002264 triphosphate group Chemical group [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 claims 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims 2
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 125000000304 alkynyl group Chemical group 0.000 claims 2
- 125000003277 amino group Chemical group 0.000 claims 2
- KWEDUNSJJZVRKR-UHFFFAOYSA-N carbononitridic azide Chemical group [N-]=[N+]=NC#N KWEDUNSJJZVRKR-UHFFFAOYSA-N 0.000 claims 2
- 238000007306 functionalization reaction Methods 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- MJGXOSYVWHETDC-UHFFFAOYSA-N methoxymethanethiol Chemical group COCS MJGXOSYVWHETDC-UHFFFAOYSA-N 0.000 claims 2
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 2
- 229910052711 selenium Inorganic materials 0.000 claims 2
- 239000011669 selenium Substances 0.000 claims 2
- 230000002194 synthesizing effect Effects 0.000 claims 2
- 239000001226 triphosphate Substances 0.000 claims 2
- 235000011178 triphosphate Nutrition 0.000 claims 2
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- -1 methaneseleno Chemical class 0.000 claims 1
- 229910052757 nitrogen Chemical group 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- 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
- C07H19/24—Heterocyclic radicals containing oxygen or sulfur as ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/102—Mutagenizing nucleic acids
- C12N15/1024—In vivo mutagenesis using high mutation rate "mutator" host strains by inserting genetic material, e.g. encoding an error prone polymerase, disrupting a gene for mismatch repair
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/22—Ribonucleases RNAses, DNAses
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6832—Enhancement of hybridisation reaction
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Plant Pathology (AREA)
- General Chemical & Material Sciences (AREA)
- Crystallography & Structural Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Saccharide Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
Claims (19)
1. Spoj koje sadrži analog nukleobaze bilo koje od sljedećih formula:
[image]
naznačeno time, da je R vodik ili reaktivni veznik koji sadrži reaktivni centar prilagođen za vezanje na transportni reagens koji sadrži isporuku i skupinu reaktivnosti komplementarnih reaktivnom centru, ili je R spojen veznik za kojeg je vezana isporuka;
gdje je svaki X ugljik,
gdje je svaki R2 nezavisno vodik, alkil, alkenil, alkinil, metoksi, metantiol, metanseleno, halogen, cijano, azidna skupina, reaktivni veznik koji sadrži reaktivni centar prilagođen za vezivanje za transportni reagens koji sadrži isporuku i skupinu reaktivnosti komplementarnu reaktivnom centru, ili spojeni veznik za kojeg je vezana isporuka,
gdje je svaki Y nezavisno sumpor, selen ili sekundarni amin,
gdje je svako E sumpor,
i valovita linija označava točku vezanja za ribozilni, deoksiribozilni ili dideoksiribozilni ostatak ili njegov analog, pri čemu je ribozilni, deoksiribozilni ili dideoksiribozilni ostatak ili njegov analog u slobodnom obliku, vezan za monofosfatnu, difosfatnu ili trifosfatnu skupinu, koja opcijski sadrži α-tiotrifosfatnu, β-tiotrifosfatnu ili γ-tiotrifosfatnu skupinu ili je uključen u RNA ili DNA ili u analog RNA ili analog DNA.
2. Spoj koje sadrži analog nukleobaze bilo koje od sljedećih formula:
[image]
gdje je svaki X nezavisno ugljik ili dušik,
gdje je svaki R1 nezavisno vodik, alkil skupina, reaktivni linker koji sadrži reaktivni centar prilagođen za vezanje za transportni reagens koji sadrži isporuku i skupinu reaktivnosti komplementarnu reaktivnom centru, ili spojen veznik za koga je vezana isporuka,
gdje je svaki R2 prisutan, kada je X ugljik i nezavisno je vodik, alkil, alkenil, alkinil, metoksi, metantiol, metanseleno, halogen, cijano, azidna skupina, reaktivni veznik koji sadrži reaktivni centar prilagođen za vezanje za transportni reagens koji sadrži isporuku i skupinu reaktivnostu komplementarnu reaktivnom centru, ili spojen veznik za kojeg je vezana isporuka,
gdje je svaki Y nezavisno sumpor, kisik, selen ili sekundarni amin,
gdje je svako E sumpor,
i valovita linija označava točku vezivanja za ribozilnu, deoksiribozilnu ili dideoksiribozilnu skupinu ili njen analog, pri čemu je ribozilni, deoksiribozilni ili dideoksiribozilni ostatak ili njegov analog u slobodnom obliku, vezan za monofosfatnu, difosfatnu ili trifosfatnu skupinu, koja opcijski sadrži α-tiotrifosfatnu, β-tiotrifosfatnu ili γ-tiotrifosfatnu skupina ili je uključen u RNA ili DNA ili u analog RNA ili analog DNA.
3. Spoj sukladno patentnom zahtjevu 1, naznačeno time, da reaktivni centar sadrži amino skupinu, acetilensku skupinu, tiol skupinu, aldehidnu skupinu ili azidnu skupinu.
4. Spoj sukladno patentnom zahtjevu 2, naznačeno time, da reaktivni centar sadrži amino skupinu, acetilensku skupinu, tiol skupinu, aldehidnu skupinu ili azidnu skupinu.
5. Spoj sukladno patentnom zahtjevu 1, naznačeno time, da ribozilni ili deoksiribozilni ostatak nosi trifosfatnu ili α-tiotrifosfatnu skupinu vezanu za njegov 5'-hidroksil.
6. Spoj sukladno patentnom zahtjevu 2, naznačeno time, da ribozilni ili deoksiribosilni ostatak nosi trifosfatnu ili α-tiotrifosfatnu skupinu vezanu za njegov 5'-hidroksil.
7. Spoj sukladno patentnom zahtjevu 1, naznačeno time, da je ribozilni ili deoksiribosilni ostatak inkorporiran u RNA ili DNA oligonukleotidni lanac, respektivno, ili je ribozilni ili deoksiribozilni ostatak ili njegov analog ugrađen u analog RNA ili DNA.
8. Spoj sukladno patentnom zahtjevu 2, naznačeno time, da je ribozilna ili deoksiribozilna grupa ugrađena u RNA ili DNA oligonukleotidni lanac, respektivno, ili je ribozilni ili deoksiribozilni ostatak ili njegov analog ugrađen u analog RNA ili DNA.
9. Spoj sukladno patentnom zahtjevu 1, naznačeno time, da najmanje jedan R2 nezavisno sadrži: skupinu odabranu iz skupine sastavljene od -C≡C-CH2NHR3 skupine, gdje je R3 vodonik ili je amino-zaštitna skupinu; acetilensku skupinu pogodnu za uporabu u reakciji brave s transportnim reagensom koji sadrži punjenje i acetilen-reaktivnu skupinu; tiol skupinu pogodnu za uporabu u reakciji s transportnim reagensom koji sadrži isporuku i tiol-reaktivnu skupinu; aldehidnu skupinu pogodnu za uporabu u reakciji s transportnim reagensom koji sadrži isporuku i aldehidnu reaktivnu skupinu; azidnu skupinu pogodnu za uporabu u reakciji s transportnim reagensom koji sadrži isporuku i azidnu reaktivnu skupinu; i -C≡C-(CH2)n-C≡CH, gde n je 1, 2, 3, 4, 5 ili 6; i -C≡C-(CH2)n1-O-(CH2)n2-C≡CH, gdje su n1 i n2 svaki nezavisno 1, 2 ili 3.
10. Spoj sukladno patentnom zahtjevu 2, naznačeno time, da najmanje jedan R2 nezavisno sadrži: skupinu odabranu od skupinu koja se sastoji od -C≡C-CH2NHR3 grupe, gdje je R3 vodonik ili je amino-zaštitna skupinu; acetilensku skupinu pogodnu za upotrebu u reakciji brave sa transportnim reagensom koji sadrži isporuku i acetilensku reaktivnu skupinu; tiol skupinu pogodnu za upotrebu u reakciji s transportnim reagensom koji sadrži isporuku i tiol-reaktivnu skupinu; aldehidnu skupinu pogodnu za uporabu u reakciji s transportnim reagensom koji sadrži isporuku i aldehidnu reaktivnu skupinu; azidnu skupinu pogodnu za uporabu u reakciji s transportnim reagensom koji sadrži isporuku i azidnu reaktivnu skupinu; i -C≡C-(CH2)n-C≡CH, gdje n je 1, 2, 3, 4, 5 ili 6; i -C≡C-(CH2)n1-O-(CH2)n2-C≡CH, gdje su n1 i n2 svaki nezavisno 1, 2 ili 3.
11. Nukleobazni par koji sadrži prvi analog nukleobaze koji sadrži formulu
[image]
i drugi analog nukleobaze koji ima bilo koju od formula
[image]
gdje je R nezavisno vodik, ili spojen veznik koji sadrži reaktivni centar prilagođen za vezanje za transportni reagens koji sadrži isporuku i skupinu reaktivnosti komplementarnu reaktivnom centru, ili je R spojen veznik za kojeg je vezana isporuka;
i valovita linija označava točku vezanja za ribozilnu, deoksiribozilnu ili dideoksiribozilnu skupinu ili njen analog, pri čemu je ribozilni, deoksiribozilni ili dideoksiribozilni ostatak ili njegov analog u slobodnom obliku, vezan za monofosfatnu, difosfatnu ili trifosfatnu skupinu, koja opcijski sadrži α-tiotrifosfatnu, β-tiotrifosfatnu ili γ-tiotrifosfatnu skupinu ili je uključen u RNA ili DNA ili u analog RNA ili analog DNA.
12. Dvolančani oligonukleotidni dupleks, naznačen time, da prvi oligonukleotidni lanac sadrži spoj sukladno patentnom zahtjevu 1, a drugi komplementarni oligonukleotidni lanac sadrži komplementarnu nukleobazu za uparivanje baze na njegovom komplementarnom položaju uparivanja baze.
13. Dvolančani oligonukleotidni dupleks, naznačen time, da prvi oligonukleotidni lanac sadrži spoj sukladno patentnom zahtjevu 2, a drugi komplementarni oligonukleotidni lanac sadrži komplementarnu nukleobazu za uparivanje baze na njegovom komplementarnom položaju za uparivanje baze.
14. Dvolančani oligonukleotidni dupleks sukladno patentnom zahtjevu 12, naznačen time, da prvi lanac sadrži nukleobazu koja ima formulu
[image]
a drugi lanac sadrži komplementarnu nukleobazu za uparivanje baze odabranu iz
[image]
na komplementarnom mjestu spajanja baze.
15. Postupak izvođenja funkcionalizacije specifične za položaj dvostruko lančanog oligonukleotidnog dupleksa, koji obuhvaća: ugradnju neprirodne nukleobaze koja sadrži reaktivni veznik koji sadrži reaktivni centar, nukleobaze koja je odabrana iz spoja sukladno patentnom zahtjevu 1, u prvi oligonukleotidni lanac; zatim, sintetiziranje drugog oligonukleotidnog lanca komplementarno prvom oligonukleotidnom lancu, drugi oligonukleotidni lanac koji sadrži nukleobazu komplementarnu neprirodnoj nukleobazi na mjestu specifičnom komplementarnom položaju u njemu, pod uvjetom da prvi oligonukleotidni lanac i drugi oligonukleotidni lanac oblikuju dvolančani oligonukleotidni dupleks; zatim, dovođenje u kontakt dvolančanog oligonukleotidnog dupleksa koji inkorporira neprirodnu nukleobazu koja sadrži reaktivnu skupinu veznika s transportnim reagensom koji sadrži isporuku i skupinu komplementarne reaktivnosti, pod uvjetima podobnim za reakciju reaktivnog veznika i skupine komplementarne reaktivnosti da bi se došlo do spojenog veznika; da bi se osigurao funkcionalni dvolančani oligonukleotidni dupleks s isporukom vezanom za njega putem spojenog veznika
16. Postupak provođenja funkcionalizacije dvostrukog lanca oligonukleotidnog dupleksa specifične za položaj, koji uključuje: ugrađivanje neprirodne nukleobaze koja sadrži reaktivni linker koji sadrži reaktivni centar, nukleobaze koja je odabrana iz spoja sukladno patentnom zahtjevu 2, u prvi oligonukleotidni lanac; zatim, sintetiziranje drugog oligonukleotidnog lanca komplementarno prvom oligonukleotidnom lancu, drugi oligonukleotidni lanac koji sadrži nukleobazu komplementarnu s neprirodnom nukleobazom na mjesto-specifičnom komplementarnom položaju u njemu, pod uvjetima da prvi oligonukleotidni lanac i drugi oligonukleotidni lanac oblikuju dvolančani oligonukleotidni dupleks; zatim, kontaktiranje dvolančanog oligonukleotidnog dupleksa koji uključuje neprirodnu nukleobazu koja sadrži reaktivni dio veznika s transportnim reagensom koji sadrži isporuku i skupinu komplementarne reaktivnosti, pod uvjetom pogodnim za reakciju reaktivnog veznika i skupine komplementarne reaktivnosti kako bi se dobio spojeni veznik; da bi se osigurao funkcionalizirani dvolančani oligonukleotidni dupleks s teretom povezanom za njega spojenim veznikom.
17. Struktura koja sadrži formulu:
N1-Zx-N2,
gdje je N1 nukleotid ili njegov analog, ili terminalna fosfatna skupina; gdje je N2 nukleotid ili njegov analog, ili terminalna hidroksilna skupina; gdje je Z spoj sukladno patentnom zahtjevu 1 ili patentnom zahtjevu 2 i gdje je x cijeli broj od 1 do 20.
18. Spoj sukladno patentnom zahtjevu 1, koje ima formulu odabranu od:
[image]
ili njegovih derivata ili analoga,
[image]
19. Spoj sukladno patentnom zahtjevu 2, odabrano iz skupine sastavljene od:
[image]
i njihovih derivata ili analoga.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361863649P | 2013-08-08 | 2013-08-08 | |
| EP14834827.9A EP3041854B1 (en) | 2013-08-08 | 2014-08-08 | A method for the site-specific enzymatic labelling of nucleic acids in vitro by incorporation of unnatural nucleotides |
| PCT/US2014/050423 WO2015021432A1 (en) | 2013-08-08 | 2014-08-08 | A method for the site-specific enzymatic labelling of nucleic acids in vitro by incorporation of unnatural nucleotides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20200250T1 true HRP20200250T1 (hr) | 2020-05-29 |
Family
ID=52461970
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20200250TT HRP20200250T1 (hr) | 2013-08-08 | 2020-02-14 | Metoda site-specifično enzimsko obilježavanje nukleinskih kiselina in vitro ugradnjom neprirodnih nukleotida |
Country Status (16)
| Country | Link |
|---|---|
| US (4) | US10626138B2 (hr) |
| EP (3) | EP3656781A1 (hr) |
| JP (4) | JP2016531122A (hr) |
| AU (4) | AU2014306271A1 (hr) |
| CA (1) | CA2920527A1 (hr) |
| DK (1) | DK3041854T3 (hr) |
| EA (2) | EA038576B1 (hr) |
| ES (1) | ES2773547T3 (hr) |
| HR (1) | HRP20200250T1 (hr) |
| HU (1) | HUE048710T2 (hr) |
| LT (1) | LT3041854T (hr) |
| PL (1) | PL3041854T3 (hr) |
| PT (1) | PT3041854T (hr) |
| RS (1) | RS59991B1 (hr) |
| SI (1) | SI3041854T1 (hr) |
| WO (1) | WO2015021432A1 (hr) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2014306271A1 (en) | 2013-08-08 | 2016-03-24 | The Scripps Research Institute | A method for the site-specific enzymatic labelling of nucleic acids in vitro by incorporation of unnatural nucleotides |
| CN105764491A (zh) | 2013-12-09 | 2016-07-13 | 度瑞公司 | 药物活性剂复合物、聚合物复合物，以及包括其的组合物和方法 |
| EP3943607A1 (en) | 2014-04-09 | 2022-01-26 | The Scripps Research Institute | Import of unnatural or modified nucleoside triphosphates into cells via nucleic acid triphosphate transporters |
| WO2017106767A1 (en) | 2015-12-18 | 2017-06-22 | The Scripps Research Institute | Production of unnatural nucleotides using a crispr/cas9 system |
| PL415967A1 (pl) * | 2016-01-29 | 2017-07-31 | Univ Warszawski | 5'-tiofosforanowe analogi końca 5' mRNA (kapu), sposób ich otrzymywania i zastosowanie |
| ES2929047T3 (es) | 2016-06-24 | 2022-11-24 | Scripps Research Inst | Transportador de nucleósido trifosfato novedoso y usos del mismo |
| AR112756A1 (es) * | 2017-07-11 | 2019-12-11 | Synthorx Inc | Incorporación de nucleótidos no naturales, y su método |
| US20200224234A1 (en) * | 2017-07-11 | 2020-07-16 | The Scripps Research Institute | Incorporation of unnatural nucleotides and methods of use in vivo thereof |
| KR20200035092A (ko) | 2017-08-03 | 2020-04-01 | 신톡스, 인크. | 자가면역 질환의 치료를 위한 사이토카인 접합체 |
| TW202045208A (zh) | 2019-02-06 | 2020-12-16 | 美商欣爍克斯公司 | Il-2結合物及其使用方法 |
| CN110478950B (zh) * | 2019-05-14 | 2021-08-06 | 江苏四新科技应用研究所股份有限公司 | 一种用于透明液体洗涤剂的消泡剂 |
| AU2020291535A1 (en) * | 2019-06-14 | 2022-01-20 | The Scripps Research Institute | Reagents and methods for replication, transcription, and translation in semi-synthetic organisms |
| TW202120128A (zh) | 2019-08-15 | 2021-06-01 | 美商欣爍克斯公司 | 使用ｉｌ－２接合物之免疫腫瘤學組合療法 |
| TW202122401A (zh) | 2019-08-23 | 2021-06-16 | 美商欣爍克斯公司 | 新穎之ｉｌ－１５接合物及其用途 |
| BR112022003335A2 (pt) | 2019-09-10 | 2022-05-24 | Synthorx Inc | Conjugados de il-2 e métodos de uso para tratar doenças autoimunes |
| TW202131952A (zh) | 2019-11-04 | 2021-09-01 | 美商欣爍克斯公司 | 介白素10接合物及其用途 |
| AU2020395113A1 (en) | 2019-12-02 | 2022-06-09 | Shape Therapeutics Inc. | Therapeutic editing |
| JP2023518105A (ja) * | 2019-12-30 | 2023-04-27 | 源點生物科技股▲フン▼有限公司 | 酵素を使用して核酸配列を調製するための方法 |
| KR20220104057A (ko) * | 2019-12-30 | 2022-07-25 | 위안디안 바이오랩스 컴퍼니 리미티드 | 효소를 이용한 핵산 서열 제조 장치 및 방법 |
| CA3183834A1 (en) | 2020-06-25 | 2021-12-30 | Giovanni Abbadessa | Immuno oncology combination therapy with il-2 conjugates and anti-egfr antibodies |
| EP4225376A1 (en) | 2020-10-09 | 2023-08-16 | Synthorx, Inc. | Immuno oncology combination therapy with il-2 conjugates and pembrolizumab |
| CA3194880A1 (en) | 2020-10-09 | 2022-04-14 | Carolina E. CAFFARO | Immuno oncology therapies with il-2 conjugates |
| WO2022123947A1 (ja) * | 2020-12-08 | 2022-06-16 | 雄大 田淵 | 中和可能コバレントドラッグ |
| EP4261285A1 (en) * | 2020-12-08 | 2023-10-18 | Yudai Tabuchi | Neutralizable covalent drug |
| WO2022174102A1 (en) | 2021-02-12 | 2022-08-18 | Synthorx, Inc. | Lung cancer combination therapy with il-2 conjugates and an anti-pd-1 antibody or antigen-binding fragment thereof |
| TW202245843A (zh) | 2021-02-12 | 2022-12-01 | 美商欣爍克斯公司 | Ｉｌ－２接合物及西米普利單抗（ｃｅｍｉｐｌｉｍａｂ）之皮膚癌組合療法 |
| WO2022256534A1 (en) | 2021-06-03 | 2022-12-08 | Synthorx, Inc. | Head and neck cancer combination therapy comprising an il-2 conjugate and pembrolizumab |
| CN117980481A (zh) | 2021-07-16 | 2024-05-03 | 阿普塔生物公司 | 用于基因表达调节的多核苷酸组合物和方法 |
| CN113759107A (zh) * | 2021-08-18 | 2021-12-07 | 苏州立禾生物医学工程有限公司 | 生物素标记缓冲液 |
| CN114196714B (zh) * | 2021-11-04 | 2023-09-29 | 华南理工大学 | 利用末端脱氧核糖核苷酸转移酶无模板合成含非天然碱基寡核苷酸链的方法及其应用 |
| CN114031648A (zh) * | 2021-11-08 | 2022-02-11 | 河南师范大学 | 一类非天然碱基三磷酸及其合成方法和应用 |
| CN114249788B (zh) * | 2021-12-17 | 2023-08-08 | 河南师范大学 | 非天然碱基核苷酸磷酸单酯类前药分子及其制备方法和应用 |
| WO2023122573A1 (en) | 2021-12-20 | 2023-06-29 | Synthorx, Inc. | Head and neck cancer combination therapy comprising an il-2 conjugate and pembrolizumab |
| WO2023122750A1 (en) | 2021-12-23 | 2023-06-29 | Synthorx, Inc. | Cancer combination therapy with il-2 conjugates and cetuximab |
Family Cites Families (202)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
| US4469863A (en) | 1980-11-12 | 1984-09-04 | Ts O Paul O P | Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof |
| US5023243A (en) | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
| US4476301A (en) | 1982-04-29 | 1984-10-09 | Centre National De La Recherche Scientifique | Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon |
| JPS5927900A (ja) | 1982-08-09 | 1984-02-14 | Wakunaga Seiyaku Kk | 固定化オリゴヌクレオチド |
| 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 |
| US4605735A (en) | 1983-02-14 | 1986-08-12 | Wakunaga Seiyaku Kabushiki Kaisha | Oligonucleotide derivatives |
| US4948882A (en) | 1983-02-22 | 1990-08-14 | Syngene, Inc. | Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis |
| US4824941A (en) | 1983-03-10 | 1989-04-25 | Julian Gordon | Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems |
| US4587044A (en) | 1983-09-01 | 1986-05-06 | The Johns Hopkins University | Linkage of proteins to nucleic acids |
| US5118802A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside |
| US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
| US5015733A (en) | 1983-12-20 | 1991-05-14 | California Institute Of Technology | Nucleosides possessing blocked aliphatic amino groups |
| US4849513A (en) | 1983-12-20 | 1989-07-18 | California Institute Of Technology | Deoxyribonucleoside phosphoramidites in which an aliphatic amino group is attached to the sugar ring and their use for the preparation of oligonucleotides containing aliphatic amino groups |
| US5550111A (en) | 1984-07-11 | 1996-08-27 | Temple University-Of The Commonwealth System Of Higher Education | Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof |
| FR2567892B1 (fr) | 1984-07-19 | 1989-02-17 | Centre Nat Rech Scient | Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons |
| US5258506A (en) | 1984-10-16 | 1993-11-02 | Chiron Corporation | Photolabile reagents for incorporation into oligonucleotide chains |
| US5430136A (en) | 1984-10-16 | 1995-07-04 | Chiron Corporation | Oligonucleotides having selectably cleavable and/or abasic sites |
| US5367066A (en) | 1984-10-16 | 1994-11-22 | Chiron Corporation | Oligonucleotides with selectably cleavable and/or abasic sites |
| ZW17385A1 (en) | 1984-11-06 | 1986-02-19 | Hoffmann La Roche | Tricyclic pyridine derivatives |
| US4828979A (en) | 1984-11-08 | 1989-05-09 | Life Technologies, Inc. | Nucleotide analogs for nucleic acid labeling and detection |
| FR2575751B1 (fr) | 1985-01-08 | 1987-04-03 | Pasteur Institut | Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques |
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US5185444A (en) | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
| US5235033A (en) | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
| US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| US5405938A (en) | 1989-12-20 | 1995-04-11 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| US4762779A (en) | 1985-06-13 | 1988-08-09 | Amgen Inc. | Compositions and methods for functionalizing nucleic acids |
| US5093232A (en) | 1985-12-11 | 1992-03-03 | Chiron Corporation | Nucleic acid probes |
| US4910300A (en) | 1985-12-11 | 1990-03-20 | Chiron Corporation | Method for making nucleic acid probes |
| US5317098A (en) | 1986-03-17 | 1994-05-31 | Hiroaki Shizuya | Non-radioisotope tagging of fragments |
| JPS638396A (ja) | 1986-06-30 | 1988-01-14 | Wakunaga Pharmaceut Co Ltd | ポリ標識化オリゴヌクレオチド誘導体 |
| US5264423A (en) | 1987-03-25 | 1993-11-23 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
| US5276019A (en) | 1987-03-25 | 1994-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
| US4904582A (en) | 1987-06-11 | 1990-02-27 | Synthetic Genetics | Novel amphiphilic nucleic acid conjugates |
| ATE113059T1 (de) | 1987-06-24 | 1994-11-15 | Florey Howard Inst | Nukleosid-derivate. |
| US5585481A (en) | 1987-09-21 | 1996-12-17 | Gen-Probe Incorporated | Linking reagents for nucleotide probes |
| US5188897A (en) | 1987-10-22 | 1993-02-23 | Temple University Of The Commonwealth System Of Higher Education | Encapsulated 2',5'-phosphorothioate oligoadenylates |
| US4924624A (en) | 1987-10-22 | 1990-05-15 | Temple University-Of The Commonwealth System Of Higher Education | 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof |
| US5525465A (en) | 1987-10-28 | 1996-06-11 | Howard Florey Institute Of Experimental Physiology And Medicine | Oligonucleotide-polyamide conjugates and methods of production and applications of the same |
| DE3738460A1 (de) | 1987-11-12 | 1989-05-24 | Max Planck Gesellschaft | Modifizierte oligonukleotide |
| US5082830A (en) | 1988-02-26 | 1992-01-21 | Enzo Biochem, Inc. | End labeled nucleotide probe |
| EP0406309A4 (en) | 1988-03-25 | 1992-08-19 | The University Of Virginia Alumni Patents Foundation | Oligonucleotide n-alkylphosphoramidates |
| US5278302A (en) | 1988-05-26 | 1994-01-11 | University Patents, Inc. | Polynucleotide phosphorodithioates |
| US5109124A (en) | 1988-06-01 | 1992-04-28 | Biogen, Inc. | Nucleic acid probe linked to a label having a terminal cysteine |
| US5216141A (en) | 1988-06-06 | 1993-06-01 | Benner Steven A | Oligonucleotide analogs containing sulfur linkages |
| US5175273A (en) | 1988-07-01 | 1992-12-29 | Genentech, Inc. | Nucleic acid intercalating agents |
| US5262536A (en) | 1988-09-15 | 1993-11-16 | E. I. Du Pont De Nemours And Company | Reagents for the preparation of 5'-tagged oligonucleotides |
| US5512439A (en) | 1988-11-21 | 1996-04-30 | Dynal As | Oligonucleotide-linked magnetic particles and uses thereof |
| US5457183A (en) | 1989-03-06 | 1995-10-10 | Board Of Regents, The University Of Texas System | Hydroxylated texaphyrins |
| US5599923A (en) | 1989-03-06 | 1997-02-04 | Board Of Regents, University Of Tx | Texaphyrin metal complexes having improved functionalization |
| US5391723A (en) | 1989-05-31 | 1995-02-21 | Neorx Corporation | Oligonucleotide conjugates |
| US4958013A (en) | 1989-06-06 | 1990-09-18 | Northwestern University | Cholesteryl modified oligonucleotides |
| US5451463A (en) | 1989-08-28 | 1995-09-19 | Clontech Laboratories, Inc. | Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides |
| US5134066A (en) | 1989-08-29 | 1992-07-28 | Monsanto Company | Improved probes using nucleosides containing 3-dezauracil analogs |
| US5254469A (en) | 1989-09-12 | 1993-10-19 | Eastman Kodak Company | Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures |
| US5591722A (en) | 1989-09-15 | 1997-01-07 | Southern Research Institute | 2'-deoxy-4'-thioribonucleosides and their antiviral activity |
| US5399676A (en) | 1989-10-23 | 1995-03-21 | Gilead Sciences | Oligonucleotides with inverted polarity |
| CA2071510C (en) | 1989-10-24 | 2004-07-06 | Chris A. Buhr | 2' modified oligonucleotides |
| US5264564A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences | Oligonucleotide analogs with novel linkages |
| US5264562A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences, Inc. | Oligonucleotide analogs with novel linkages |
| US5292873A (en) | 1989-11-29 | 1994-03-08 | The Research Foundation Of State University Of New York | Nucleic acids labeled with naphthoquinone probe |
| US5177198A (en) | 1989-11-30 | 1993-01-05 | University Of N.C. At Chapel Hill | Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates |
| US5130302A (en) | 1989-12-20 | 1992-07-14 | Boron Bilogicals, Inc. | Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same |
| US5486603A (en) | 1990-01-08 | 1996-01-23 | Gilead Sciences, Inc. | Oligonucleotide having enhanced binding affinity |
| US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
| US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
| US5578718A (en) | 1990-01-11 | 1996-11-26 | Isis Pharmaceuticals, Inc. | Thiol-derivatized nucleosides |
| US5587470A (en) | 1990-01-11 | 1996-12-24 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
| US5681941A (en) | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
| US5459255A (en) | 1990-01-11 | 1995-10-17 | Isis Pharmaceuticals, Inc. | N-2 substituted purines |
| US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
| US5214136A (en) | 1990-02-20 | 1993-05-25 | Gilead Sciences, Inc. | Anthraquinone-derivatives oligonucleotides |
| WO1991013080A1 (en) | 1990-02-20 | 1991-09-05 | Gilead Sciences, Inc. | Pseudonucleosides and pseudonucleotides and their polymers |
| US5321131A (en) | 1990-03-08 | 1994-06-14 | Hybridon, Inc. | Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling |
| WO1991014781A1 (en) | 1990-03-19 | 1991-10-03 | Henkel Research Corporation | METHOD FOR INCREASING THE OMEGA-HYDROXYLASE ACTIVITY IN $i(CANDIDA TROPICALIS) |
| US5470967A (en) | 1990-04-10 | 1995-11-28 | The Dupont Merck Pharmaceutical Company | Oligonucleotide analogs with sulfamate linkages |
| GB9009980D0 (en) | 1990-05-03 | 1990-06-27 | Amersham Int Plc | Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides |
| DK0455905T3 (da) | 1990-05-11 | 1998-12-07 | Microprobe Corp | Dipsticks til nukleinsyrehybridiseringsassays og fremgangsmåde til kovalent immobilisering af oligonukleotider |
| US5677437A (en) | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
| US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
| US5688941A (en) | 1990-07-27 | 1997-11-18 | Isis Pharmaceuticals, Inc. | Methods of making conjugated 4' desmethyl nucleoside analog compounds |
| US5618704A (en) | 1990-07-27 | 1997-04-08 | Isis Pharmacueticals, Inc. | Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling |
| US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
| US5218105A (en) | 1990-07-27 | 1993-06-08 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
| JPH0874B2 (ja) | 1990-07-27 | 1996-01-10 | アイシス・ファーマシューティカルス・インコーポレーテッド | 遺伝子発現を検出および変調するヌクレアーゼ耐性、ピリミジン修飾オリゴヌクレオチド |
| US5623070A (en) | 1990-07-27 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| US5138045A (en) | 1990-07-27 | 1992-08-11 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
| US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
| US5541307A (en) | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
| US5245022A (en) | 1990-08-03 | 1993-09-14 | Sterling Drug, Inc. | Exonuclease resistant terminally substituted oligonucleotides |
| WO1992002534A2 (en) | 1990-08-03 | 1992-02-20 | Sterling Drug, Inc. | Compounds and methods for inhibiting gene expression |
| US5177196A (en) | 1990-08-16 | 1993-01-05 | Microprobe Corporation | Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof |
| US5512667A (en) | 1990-08-28 | 1996-04-30 | Reed; Michael W. | Trifunctional intermediates for preparing 3'-tailed oligonucleotides |
| US5214134A (en) | 1990-09-12 | 1993-05-25 | Sterling Winthrop Inc. | Process of linking nucleosides with a siloxane bridge |
| US5561225A (en) | 1990-09-19 | 1996-10-01 | Southern Research Institute | Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages |
| WO1992005186A1 (en) | 1990-09-20 | 1992-04-02 | Gilead Sciences | Modified internucleoside linkages |
| NZ239893A (en) | 1990-09-25 | 1993-11-25 | Hoechst Japan | A method for introducing a foreign dna into a cell |
| US5432272A (en) | 1990-10-09 | 1995-07-11 | Benner; Steven A. | Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases |
| ATE198598T1 (de) | 1990-11-08 | 2001-01-15 | Hybridon Inc | Verbindung von mehrfachreportergruppen auf synthetischen oligonukleotiden |
| US5672697A (en) | 1991-02-08 | 1997-09-30 | Gilead Sciences, Inc. | Nucleoside 5'-methylene phosphonates |
| US5719262A (en) | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
| US5714331A (en) | 1991-05-24 | 1998-02-03 | Buchardt, Deceased; Ole | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
| US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
| US5371241A (en) | 1991-07-19 | 1994-12-06 | Pharmacia P-L Biochemicals Inc. | Fluorescein labelled phosphoramidites |
| US5571799A (en) | 1991-08-12 | 1996-11-05 | Basco, Ltd. | (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response |
| EP0538194B1 (de) | 1991-10-17 | 1997-06-04 | Novartis AG | Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte |
| US5594121A (en) | 1991-11-07 | 1997-01-14 | Gilead Sciences, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified purines |
| EP0637965B1 (en) | 1991-11-26 | 2002-10-16 | Isis Pharmaceuticals, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines |
| TW393513B (en) | 1991-11-26 | 2000-06-11 | Isis Pharmaceuticals Inc | Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines |
| US5484908A (en) | 1991-11-26 | 1996-01-16 | Gilead Sciences, Inc. | Oligonucleotides containing 5-propynyl pyrimidines |
| US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
| US5595726A (en) | 1992-01-21 | 1997-01-21 | Pharmacyclics, Inc. | Chromophore probe for detection of nucleic acid |
| US5565552A (en) | 1992-01-21 | 1996-10-15 | Pharmacyclics, Inc. | Method of expanded porphyrin-oligonucleotide conjugate synthesis |
| FR2687679B1 (fr) | 1992-02-05 | 1994-10-28 | Centre Nat Rech Scient | Oligothionucleotides. |
| US5633360A (en) | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
| US5434257A (en) | 1992-06-01 | 1995-07-18 | Gilead Sciences, Inc. | Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages |
| EP0577558A2 (de) | 1992-07-01 | 1994-01-05 | Ciba-Geigy Ag | Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte |
| US5272250A (en) | 1992-07-10 | 1993-12-21 | Spielvogel Bernard F | Boronated phosphoramidate compounds |
| RU95114435A (ru) | 1992-12-14 | 1997-05-20 | Ханивелл Инк. (Us) | Система с бесщеточным двигателем постоянного тока |
| US5574142A (en) | 1992-12-15 | 1996-11-12 | Microprobe Corporation | Peptide linkers for improved oligonucleotide delivery |
| US5476925A (en) | 1993-02-01 | 1995-12-19 | Northwestern University | Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups |
| GB9304618D0 (en) | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Chemical compounds |
| DK0691968T3 (da) | 1993-03-30 | 1998-02-23 | Sanofi Sa | Acykliske nukleosid-analoge og oligonukleotidsekvenser indeholdende disse |
| EP0691977B1 (en) | 1993-03-31 | 1997-11-26 | Sanofi | Oligonucleotides with amide linkages replacing phosphodiester linkages |
| EP0691979A1 (en) | 1993-03-31 | 1996-01-17 | Sanofi | Novel 5'-substituted nucleosides and oligomers produced therefrom |
| DE4311944A1 (de) | 1993-04-10 | 1994-10-13 | Degussa | Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen |
| GB9311682D0 (en) | 1993-06-05 | 1993-07-21 | Ciba Geigy Ag | Chemical compounds |
| US5502177A (en) | 1993-09-17 | 1996-03-26 | Gilead Sciences, Inc. | Pyrimidine derivatives for labeled binding partners |
| US5457187A (en) | 1993-12-08 | 1995-10-10 | Board Of Regents University Of Nebraska | Oligonucleotides containing 5-fluorouracil |
| US5446137B1 (en) | 1993-12-09 | 1998-10-06 | Behringwerke Ag | Oligonucleotides containing 4'-substituted nucleotides |
| US5519134A (en) | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
| US5596091A (en) | 1994-03-18 | 1997-01-21 | The Regents Of The University Of California | Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides |
| US5627053A (en) | 1994-03-29 | 1997-05-06 | Ribozyme Pharmaceuticals, Inc. | 2'deoxy-2'-alkylnucleotide containing nucleic acid |
| US5625050A (en) | 1994-03-31 | 1997-04-29 | Amgen Inc. | Modified oligonucleotides and intermediates useful in nucleic acid therapeutics |
| US5525711A (en) | 1994-05-18 | 1996-06-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Pteridine nucleotide analogs as fluorescent DNA probes |
| US5597696A (en) | 1994-07-18 | 1997-01-28 | Becton Dickinson And Company | Covalent cyanine dye oligonucleotide conjugates |
| US5597909A (en) | 1994-08-25 | 1997-01-28 | Chiron Corporation | Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use |
| US5580731A (en) | 1994-08-25 | 1996-12-03 | Chiron Corporation | N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith |
| GB9606158D0 (en) | 1996-03-23 | 1996-05-29 | Ciba Geigy Ag | Chemical compounds |
| US7875733B2 (en) | 2003-09-18 | 2011-01-25 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising 4′-thionucleosides for use in gene modulation |
| AU6024998A (en) | 1997-01-15 | 1998-08-07 | Glycomed Incorporated | Aryl c-glycoside compounds and sulfated esters thereof |
| US6770748B2 (en) | 1997-03-07 | 2004-08-03 | Takeshi Imanishi | Bicyclonucleoside and oligonucleotide analogue |
| JP3756313B2 (ja) | 1997-03-07 | 2006-03-15 | 武 今西 | 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体 |
| US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
| EP1557424A1 (en) | 1997-09-12 | 2005-07-27 | Exiqon A/S | Bi-cyclic nucleoside, nucleotide and oligonucleoide analogues |
| US6955807B1 (en) | 1998-05-15 | 2005-10-18 | Bayer Pharmaceuticals Corporation | IL-2 selective agonists and antagonists |
| US6562798B1 (en) | 1998-06-05 | 2003-05-13 | Dynavax Technologies Corp. | Immunostimulatory oligonucleotides with modified bases and methods of use thereof |
| US6175001B1 (en) * | 1998-10-16 | 2001-01-16 | The Scripps Research Institute | Functionalized pyrimidine nucleosides and nucleotides and DNA's incorporating same |
| NZ514348A (en) | 1999-05-04 | 2004-05-28 | Exiqon As | L-ribo-LNA analogues |
| US6525191B1 (en) | 1999-05-11 | 2003-02-25 | Kanda S. Ramasamy | Conformationally constrained L-nucleosides |
| US7101992B1 (en) | 1999-07-15 | 2006-09-05 | Japan Science And Technology Agency | Nucleic acid base pair |
| AU1239901A (en) | 1999-10-29 | 2001-05-14 | Stratagene | Compositions and methods utilizing dna polymerases |
| WO2002062816A1 (en) | 2001-02-07 | 2002-08-15 | Celltech R & D Limited | Non-natural nucleotides and dinucleotides |
| MXPA03007853A (es) | 2001-03-01 | 2004-05-24 | Pharmasset Ltd | Metodo para la sintesis de 2',3'-didesoxi-2',3'-dideshidronucleosidos. |
| AUPR975201A0 (en) * | 2001-12-24 | 2002-01-24 | Unisearch Limited | Enzymatic redox labelling of nucleic acids |
| US20060074035A1 (en) | 2002-04-17 | 2006-04-06 | Zhi Hong | Dinucleotide inhibitors of de novo RNA polymerases for treatment or prevention of viral infections |
| EP1544294B8 (en) | 2002-07-17 | 2014-03-19 | Riken | Nucleosides or nucleotides having novel unnatural bases and use thereof |
| CA2504694C (en) | 2002-11-05 | 2013-10-01 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
| AU2003290596B2 (en) | 2002-11-05 | 2011-05-12 | Isis Pharmaceuticals, Inc. | Sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
| WO2004106356A1 (en) | 2003-05-27 | 2004-12-09 | Syddansk Universitet | Functionalized nucleotide derivatives |
| EP1661905B9 (en) | 2003-08-28 | 2012-12-19 | IMANISHI, Takeshi | Novel artificial nucleic acids of n-o bond crosslinkage type |
| JP4956802B2 (ja) | 2003-09-10 | 2012-06-20 | 独立行政法人理化学研究所 | 非天然型塩基を有するヌクレオシド又はヌクレオチド及びその利用 |
| US7348146B2 (en) * | 2003-10-02 | 2008-03-25 | Epoch Biosciences, Inc. | Single nucleotide polymorphism analysis of highly polymorphic target sequences |
| DK2145956T3 (da) | 2003-11-03 | 2015-09-21 | Medical Res Council | Polymerase |
| BRPI0507169A (pt) | 2004-02-02 | 2007-06-26 | Ambrx Inc | polipeptìdeos do hormÈnio de crescimento humano modificados e seu usos |
| WO2006049297A1 (ja) | 2004-11-08 | 2006-05-11 | Riken | 新規なヌクレオシド若しくはヌクレオチド誘導体及びその利用 |
| JP5649018B2 (ja) | 2005-08-04 | 2015-01-07 | タグシクス・バイオ株式会社 | 新規人工塩基対及びその利用 |
| KR101404374B1 (ko) | 2005-12-09 | 2014-06-09 | 도꾸리쯔교세이호징 리가가쿠 겐큐소 | 핵산의 복제방법 및 신규한 인공 염기쌍 |
| DK1984381T3 (da) | 2006-01-27 | 2010-11-01 | Isis Pharmaceuticals Inc | 6-modificerede bicycliske nukleinsyreanaloger |
| WO2007085485A2 (en) * | 2006-01-27 | 2007-08-02 | Santaris Pharma A/S | Lna modified phosphorothiolated oligonucleotides |
| BRPI0707722A2 (pt) | 2006-02-14 | 2011-05-10 | Basf Se | compostos, processo para a preparaÇço de compostos, composiÇço agrÍcola, uso de compostos, mÉtodos para combater fungos fitopatogÊnicos, para combater pestes artràpedes, para proteger culturas de ataque ou infestaÇço por pestes artràpedes, para proteger sementes da infestaÇço por pestes artràpedes e das raÍzes e rebentos de mudas da infestaÇço por pestes artràpodes, e para proteger materiais nço-vivos do ataque ou infestaÇço por pestes artràpedes, e, semente |
| EP1992698B1 (en) | 2006-02-22 | 2018-09-05 | Riken | METHOD FOR SYNTHESIS OF SUPPRESSOR tRNA, DNA CONSTRUCT, AND PRODUCTION OF PROTEIN HAVING NON-NATURAL AMINO ACID INTEGRATED THEREIN BY USING THE DNA CONSTRUCT |
| US20140314864A1 (en) | 2006-03-31 | 2014-10-23 | Massachusetts Institute Of Technology | System for Targeted Delivery of Therapeutic Agents |
| CA2651453C (en) | 2006-05-11 | 2014-10-14 | Isis Pharmaceuticals, Inc. | 5'-modified bicyclic nucleic acid analogs |
| EP2126083A1 (en) * | 2006-12-06 | 2009-12-02 | Erik Bjerregaard Pedersen | Hoogsteen-type triplex formation of pyrene labelled probes for nucleic acid detection in fluorescence assay |
| EP2125852B1 (en) | 2007-02-15 | 2016-04-06 | Ionis Pharmaceuticals, Inc. | 5'-substituted-2'-f modified nucleosides and oligomeric compounds prepared therefrom |
| KR101551985B1 (ko) | 2007-03-09 | 2015-09-09 | 리가가쿠 겐큐쇼 | 모노뉴클레오시드 또는 모노뉴클레오티드로부터 유도되는 구조를 갖는 화합물, 핵산, 표지 물질, 핵산 검출 방법 및 키트 |
| US8278425B2 (en) | 2007-05-30 | 2012-10-02 | Isis Pharmaceuticals, Inc. | N-substituted-aminomethylene bridged bicyclic nucleic acid analogs |
| DK2173760T4 (en) | 2007-06-08 | 2016-02-08 | Isis Pharmaceuticals Inc | Carbocyclic bicyclic nukleinsyreanaloge |
| US8278283B2 (en) | 2007-07-05 | 2012-10-02 | Isis Pharmaceuticals, Inc. | 6-disubstituted or unsaturated bicyclic nucleic acid analogs |
| US8546556B2 (en) | 2007-11-21 | 2013-10-01 | Isis Pharmaceuticals, Inc | Carbocyclic alpha-L-bicyclic nucleic acid analogs |
| KR101556426B1 (ko) | 2008-03-31 | 2015-10-02 | 탁시스 바이오 가부시키가이샤 | 고선택ㆍ고효율로 ｐｃｒ 증폭이 가능한 신규 ｄｎａ |
| US8501805B2 (en) | 2008-09-24 | 2013-08-06 | Isis Pharmaceuticals, Inc. | Substituted alpha-L-bicyclic nucleosides |
| US8895712B2 (en) | 2009-10-06 | 2014-11-25 | Riken | Artificial base pair capable of forming specific base pair |
| EP2625186B1 (en) | 2010-04-28 | 2016-07-27 | Ionis Pharmaceuticals, Inc. | 5' modified nucleosides and oligomeric compounds prepared therefrom |
| KR102591732B1 (ko) | 2010-11-12 | 2023-10-19 | 넥타르 테라퓨틱스 | Ｉｌ-2 부분 및 중합체의 접합체 |
| DK3489255T3 (da) | 2011-02-10 | 2021-08-23 | Roche Glycart Ag | Muterede interleukin-2-polypeptider |
| US8343752B2 (en) | 2011-05-03 | 2013-01-01 | Verdezyne, Inc. | Biological methods for preparing adipic acid |
| AU2014306271A1 (en) * | 2013-08-08 | 2016-03-24 | The Scripps Research Institute | A method for the site-specific enzymatic labelling of nucleic acids in vitro by incorporation of unnatural nucleotides |
| EP3943607A1 (en) | 2014-04-09 | 2022-01-26 | The Scripps Research Institute | Import of unnatural or modified nucleoside triphosphates into cells via nucleic acid triphosphate transporters |
| US20170369871A1 (en) | 2015-01-12 | 2017-12-28 | Synthorx, Inc. | Incorporation of unnatural nucleotides and methods thereof |
| WO2017106767A1 (en) | 2015-12-18 | 2017-06-22 | The Scripps Research Institute | Production of unnatural nucleotides using a crispr/cas9 system |
| ES2929047T3 (es) | 2016-06-24 | 2022-11-24 | Scripps Research Inst | Transportador de nucleósido trifosfato novedoso y usos del mismo |
| US20200224234A1 (en) | 2017-07-11 | 2020-07-16 | The Scripps Research Institute | Incorporation of unnatural nucleotides and methods of use in vivo thereof |
| AR112756A1 (es) | 2017-07-11 | 2019-12-11 | Synthorx Inc | Incorporación de nucleótidos no naturales, y su método |
| MA51430A (fr) | 2017-12-29 | 2020-11-04 | Scripps Research Inst | Compositions de paire de bases non naturelles et procédés d'utilisation |
| AU2020291535A1 (en) | 2019-06-14 | 2022-01-20 | The Scripps Research Institute | Reagents and methods for replication, transcription, and translation in semi-synthetic organisms |
| WO2021067313A1 (en) | 2019-09-30 | 2021-04-08 | The Scripps Research Institute | Eukaryotic semi-synthetic organisms |
| TW202128996A (zh) | 2019-10-10 | 2021-08-01 | 美商史基普研究協會 | 用於活體內合成非天然多肽的組合物及方法 |
| AU2021364920A1 (en) | 2020-10-23 | 2023-06-22 | Synthorx, Inc. | Reverse transcription of polynucleotides comprising unnatural nucleotides |
-
2014
- 2014-08-08 AU AU2014306271A patent/AU2014306271A1/en not_active Abandoned
- 2014-08-08 US US14/910,203 patent/US10626138B2/en active Active
- 2014-08-08 DK DK14834827.9T patent/DK3041854T3/da active
- 2014-08-08 ES ES14834827T patent/ES2773547T3/es active Active
- 2014-08-08 EA EA201690274A patent/EA038576B1/ru unknown
- 2014-08-08 PT PT148348279T patent/PT3041854T/pt unknown
- 2014-08-08 EP EP19204863.5A patent/EP3656781A1/en not_active Withdrawn
- 2014-08-08 EA EA202191796A patent/EA202191796A2/ru unknown
- 2014-08-08 CA CA2920527A patent/CA2920527A1/en active Pending
- 2014-08-08 HU HUE14834827A patent/HUE048710T2/hu unknown
- 2014-08-08 LT LTEP14834827.9T patent/LT3041854T/lt unknown
- 2014-08-08 RS RS20200210A patent/RS59991B1/sr unknown
- 2014-08-08 EP EP14834827.9A patent/EP3041854B1/en active Active
- 2014-08-08 JP JP2016533480A patent/JP2016531122A/ja active Pending
- 2014-08-08 SI SI201431499T patent/SI3041854T1/sl unknown
- 2014-08-08 PL PL14834827T patent/PL3041854T3/pl unknown
- 2014-08-08 EP EP22164419.8A patent/EP4079745A1/en active Pending
- 2014-08-08 WO PCT/US2014/050423 patent/WO2015021432A1/en active Application Filing
-
2018
- 2018-11-02 AU AU2018256647A patent/AU2018256647B2/en active Active
-
2019
- 2019-05-31 JP JP2019103109A patent/JP7334069B2/ja active Active
- 2019-07-22 US US16/518,715 patent/US11634451B2/en active Active
- 2019-08-08 US US16/535,992 patent/US20200017540A1/en not_active Abandoned
-
2020
- 2020-02-14 HR HRP20200250TT patent/HRP20200250T1/hr unknown
- 2020-10-15 AU AU2020256391A patent/AU2020256391B2/en active Active
-
2021
- 2021-09-10 JP JP2021147954A patent/JP7383674B2/ja active Active
-
2023
- 2023-02-06 AU AU2023200611A patent/AU2023200611A1/en active Pending
- 2023-02-22 US US18/112,952 patent/US20240101590A1/en active Pending
- 2023-08-17 JP JP2023133115A patent/JP2023179406A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HRP20200250T1 (hr) | Metoda site-specifično enzimsko obilježavanje nukleinskih kiselina in vitro ugradnjom neprirodnih nukleotida | |
| JP2020503049A5 (hr) | ||
| ES2875557T3 (es) | Enlazadores de nucleótidos modificados | |
| US20160348109A1 (en) | Post-synthetic chemical modification of rna at the 2'-position of the ribose ring via "click" chemistry | |
| NZ600183A (en) | Method for efficient exon (44) skipping in duchenne muscular dystrophy and associated means | |
| FI4104687T3 (fi) | Koostumuksia ja menetelmiä 5-huputettujen RNA:iden syntetisoimiseksi | |
| HRP20231505T1 (hr) | Oligonukleotidni pripravci i postupci pripreme istih | |
| WO2008016909A3 (en) | Nucleotide analogs | |
| CN109311925A (zh) | 立体限定的氧杂氮杂磷杂环戊烷亚磷酰胺单体与核苷或寡核苷酸的增强的偶联 | |
| JP2007504830A5 (hr) | ||
| WO2009135093A3 (en) | Rnase-h-based assays utilizing modified rna monomers | |
| JP2004117376A (ja) | Ｔａｇライブラリー化合物、組成物、キットおよび使用の方法 | |
| EP2553123A4 (en) | METHOD FOR REINFORCING NUCLEIC ACID HYBRIDIZATION | |
| AR066625A1 (es) | Analogos de oligonucleotidos modificados por fosfato con actividad inmunoestimuladora aumentada | |
| MX2009008081A (es) | Generacion de moleculas de acido nucleico. | |
| ES2586599T3 (es) | Ensayo para cribar compuestos que disminuyen selectivamente el número de células madre de cáncer | |
| Song et al. | Iminodipropionic Acid as the Leaving Group for DNA Polymerization by HIV‐1 Reverse Transcriptase | |
| Giraut et al. | Iminodiacetic-phosphoramidates as metabolic prototypes for diversifying nucleic acid polymerization in vivo | |
| ATE536360T1 (de) | Neues nukleinsäuretransfersystem | |
| Kim et al. | Two-step synthesis of 5′-deoxy-5′-thioguanosine-5′-monophosphorothioate and its incorporation efficiency into 5′-terminus of RNA for preparation of thiol-functionalized RNA | |
| Sasaki | Development of novel functional molecules targeting DNA and RNA | |
| US12012432B2 (en) | Nucleic acid complex, method for forming nucleic acid hybridization, pharmaceutical composition, nucleic acid probe, and complementary-strand nucleic acid complex | |
| ES2271036T3 (es) | Analogos de bases. | |
| US11254982B2 (en) | Osmiumtetroxide-based conversion of RNA and DNA containing thiolated nucleotides | |
| Dolinnaya et al. | Design and Synthesis of 2'-Functionalised Oligonucleotides. Their Application for Covalent Trapping the Protein-DNA Complexes |