DK2748357T3 - Fremgangsmåder til mærkning af DNA-kodede biblioteker - Google Patents
Fremgangsmåder til mærkning af DNA-kodede biblioteker Download PDFInfo
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- DK2748357T3 DK2748357T3 DK12830083.7T DK12830083T DK2748357T3 DK 2748357 T3 DK2748357 T3 DK 2748357T3 DK 12830083 T DK12830083 T DK 12830083T DK 2748357 T3 DK2748357 T3 DK 2748357T3
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- DK
- Denmark
- Prior art keywords
- nucleotides
- ligation
- tag
- headpiece
- building block
- Prior art date
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- HRLUZSSGBKDEGK-QMMMGPOBSA-N tert-butyl (2s)-2-(azidomethyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1CN=[N+]=[N-] HRLUZSSGBKDEGK-QMMMGPOBSA-N 0.000 description 1
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Classifications
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- 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
- C12N15/1034—Isolating an individual clone by screening libraries
- C12N15/1065—Preparation or screening of tagged libraries, e.g. tagged microorganisms by STM-mutagenesis, tagged polynucleotides, gene tags
-
- 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
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- 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
- C12N15/1034—Isolating an individual clone by screening libraries
- C12N15/1068—Template (nucleic acid) mediated chemical library synthesis, e.g. chemical and enzymatical DNA-templated organic molecule synthesis, libraries prepared by non ribosomal polypeptide synthesis [NRPS], DNA/RNA-polymerase mediated polypeptide synthesis
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- 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
- C12N15/1034—Isolating an individual clone by screening libraries
- C12N15/1093—General methods of preparing gene libraries, not provided for in other subgroups
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- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B50/00—Methods of creating libraries, e.g. combinatorial synthesis
- C40B50/14—Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
- C40B50/16—Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support involving encoding steps
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/11—Compounds covalently bound to a solid support
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
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- Engineering & Computer Science (AREA)
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- Biomedical Technology (AREA)
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- General Health & Medical Sciences (AREA)
- Crystallography & Structural Chemistry (AREA)
- Bioinformatics & Computational Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Structural Engineering (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
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Claims (14)
1. Fremgangsmåde til mærkning af et første bibliotek omfattende en oligonukleotid-kodet kemisk enhed, hvilken fremgangsmåde omfatter: (i) tilvejebringelse af et hovedstykke bestående af et enkeltstrenget oligonukleotid med en første funktionel gruppe og en anden funktionel gruppe, hvor hovedstykket omfatter i det mindste ét terminal 2'-substitueret nukleotid omfattende den anden funktionelle gruppe, hvor hovedstykket omfatter et 2'-substitueret nukleotid ved 5'-terminus og/eller 3'-terminus; (ii) binding af den første funktionelle gruppe i hovedstykket til en første komponent af den kemiske enhed, hvor hovedstykket er direkte forbundet med den første komponent eller hovedstykket er indirekte forbundet med den første komponent via en bifunktionel forbindelse; og (iii) ligatering af den anden funktionelle gruppe i hovedstykket til en første byggeblokmarkør bestående af et enkeltstrenget oligonukleotid for dannelse af et kompleks, hvor den første byggeblokmarkør omfatter et terminal 2'-substitueret nukleotid ved 5'-terminus og 3'-terminus, og ligateringen omfatter enzymatisk ligation; hvor trinene (ii) og (iii) kan udføres i en vilkårlig rækkefølge, og hvor den første byggeblokmarkør koder for bindingsreaktionen i trin (ii), hvorved der tilvejebringes et markeret bibliotek.
2. Fremgangsmåde ifølge krav 1, hvor de nævnte 2'-substituerede nukleotider er et 2'-O-methyl-nukleotid eller et 2-fluor-nukleotid.
3. Fremgangsmåde ifølge krav 1 eller 2, hvor de nævnte 2'-substituerede nukleotider er 2'-0-methylguanin, 2'-0-methyluracil, 2'-0-methyladenosin, 2'-0-methylthymidin, 2'-0-methylinosin, 2'-0-methylcytidin, 2'-0-methyldiaminopurin, 2'-fluorguanin, 2'-fluoruracil, 2'-fluoradenosin, 2'-fluorthymidin, 2'-fluorinosin, 2'-fluorcytidin eller 2'-fluordiaminopurin.
4. Fremgangsmåde ifølge ethvert af kravene 1-3, hvor trin (ii) omfatter binding af hovedstykket direkte til den første komponent.
5. Fremgangsmåde ifølge ethvert af kravene 1-3, hvor trin (ii) omfatter binding af hovedstykket indirekte til den første komponent via en bifunktionel forbindelse.
6. Fremgangsmåde ifølge ethvert af kravene 1-5, som yderligere omfatter (iv) binding af en anden byggeblokmarkør bestående af et enkeltstrenget oligo-nukleotid til 5'-terminus eller 3'-terminus af komplekset; og (v) binding af en anden komponent af det kemiske bibliotek til den første komponent, hvor trinene (iv) og (v) kan udføres i en vilkårlig rækkefølge.
7. Fremgangsmåde ifølge krav 6, hvor den anden byggeblokmarkør omfatter et terminal 2'-substitueret nukleotid ved den ene eller flere af 5'-terminus, 3'-terminus eller den indre position af den anden byggeblokmarkør.
8. Fremgangsmåde ifølge ethvert af kravene 1-7, hvor trinet (iii) og/eller trin (iv), hvis dette foreligger, omfatter en RNA-ligase og/eller en DNA-ligase for at binde den anden byggeblokmarkør til komplekset og/eller omfatter polyethylenglycol og/eller en eller flere opløselige multivalente kationer.
9. Fremgangsmåde ifølge ethvert af kravene 1-8, hvor fremgangsmåden yderligere omfatter separering af komplekset fra eventuelle ikke-reagerede markører eller ikke-reagerede hovedstykker før ethvert af bindingstrinene (ii)-(v) og/eller oprensning af komplekset før ethvert af bindingstrinene (ii)-(v).
10. Fremgangsmåde ifølge ethvert af kravene 1-9, hvor fremgangsmåden yderligere omfatter binding af en eller flere yderligere byggeblokmarkører til komplekset og binding af en eller flere yderligere komponenter til komplekset.
11. Fremgangsmåde ifølge ethvert af kravene 1-10, hvor hovedstykket omfatter en hårnålestruktur.
12. Fremgangsmåde ifølge ethvert af kravene 1-11, hvor hovedstykket, den første byggeblokmarkør, den anden byggeblokmarkør og/eller den ene eller flere yderligere byggeblokmarkører, hvis disse foreligger, yderligere omfatter en første bibliotek-identificerende sekvens, en brugssekvens og/eller en oprindelsessekvens.
13. Fremgangsmåde ifølge ethvert af kravene 1-12, hvor fremgangsmåden yderligere omfatter binding af en første bibliotek-identificerende markør, en anvendelsessekvens, en oprindelsessekvens og/eller et halestykke til komplekset.
14. Fremgangsmåde ifølge ethvert af kravene 1-13, hvor fremgangsmåden omfatter adskillige hovedstykker.
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