초록 ▼

Nucleic acid labeling compounds are disclosed. The compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofuranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mec

Nucleic acid labeling compounds are disclosed. The compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofuranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.

대표청구항 ▼

1. A nucleic acid labeling compound represented by the structure wherein:A is hydrogen, monophosphate, diphosphate, triphosphate, α-thiotriphosphate, phosphoramidite, or H-phosphonate;X1 is O, S, NR1, or CHR2, wherein R1 and R2 are, independently, hydrogen, alkyl, or aryl;R15 is hydrogen, alkyl, or

1. A nucleic acid labeling compound represented by the structure wherein:A is hydrogen, monophosphate, diphosphate, triphosphate, α-thiotriphosphate, phosphoramidite, or H-phosphonate;X1 is O, S, NR1, or CHR2, wherein R1 and R2 are, independently, hydrogen, alkyl, or aryl;R15 is hydrogen, alkyl, or aryl;Y1 is hydrogen, N3, F, OR9, SR9, or NHR9, wherein R9 is hydrogen, alkyl, or aryl;Z1 is hydrogen, N3, F, OR9, SR9, or NHR10, wherein R10 is hydrogen, alkyl, or aryl;one of Y1 or Z1 is a group having the formula —X2L-M-Q;X2 is O, S, or NR16, wherein R16 is hydrogen, alkyl, or aryl;L is a linker moiety that is sterically and electronically suitable for incorporation into a nucleic acid;Q is a detectable moiety selected from the group consisting of biotin, carboxyfluorescein, colloidal gold, radiolabels, magnetic particles, fluorescent labels, chemiluminescent or bioluminescent labels, spin labels, dyes, and colored beads; andM is a connecting group comprising a structure that does not interfere with the nucleic acid labeling compound's function. 2. The nucleic acid labeling compound of claim 1, wherein: L is selected from the group consisting of amido alkyl, functionalized alkyl, alkenyl alkyl, alkanoyl, and N-alkyl amido. 3. The nucleic acid labeling compound of claim 1, wherein: M is selected from the group consisting of amino alkyl, —CO(CH2)5NH—, —CO—, —NH—, —CO(O)—, —CO(NH)—, —(CH2)iO—, —(CH2)jNH—, —C(O)(CH2)hO—, —CO(CH2)5NHCO(CH2)5NH—, —NH(CH2CH2O)kNH—, and —CO(CH2)5—, wherein h, i, j, and k are independently integers from 1 to 5. 4. The nucleic acid labeling compound of claim 1, wherein: Y1 is selected from the group consisting of hydrogen, OR9, wherein R9 is hydrogen or alkyl, —NR16-L-(M)m-Q, wherein R16 is hydrogen, alkyl, or aryl, —O-L-(M)m-Q, and —S-L-(M)m-Q. 5. The nucleic acid labeling compound of claim 1, wherein: Z1 is selected from the group consisting of hydrogen, OR10, wherein R10 is hydrogen or alkyl, —NR16-L-(M)m-Q, wherein R16 is hydrogen or alkyl, —O-L-(M)m-Q, and —S-L-(M)m-Q. 6. The nucleic acid labeling compound of claim 1, wherein Q is: a fluorescent group which absorbs light with a wavelength above 300 nm, and emits light with a wavelength above 310 nm, ora fluorescent group which absorbs light with a wavelength above 400 nm, and emits light with a wavelength above 410 nm. 7. The nucleic acid labeling compound of claim 1, wherein: A is H or H4O9P3—;X1 is O;Y1 is hydrogen, OR9, wherein R9 is hydrogen or alkyl, or —NR16-L-(M)m-Q, wherein R16 is hydrogen, alkyl, or aryl;Z1 is hydrogen, OR10, wherein R10 is hydrogen or alkyl, or —NR16-L-(M)m-Q, wherein R16 is hydrogen or alkyl;L is selected from the group consisting of amido alkyl, functionalized alkyl, alkenyl alkyl, alkanoyl, and N-alkyl amido;R15 is hydrogen or alkyl;M is selected from the group consisting of amino alkyl, —CO(CH2)5NH—, —CO—, —NH—, —CO(O)—, —CO(NH)—, —(CH2)iO—, —(CH2)jNH—, —C(O)(CH2)hO—, —CO(CH2)5NHCO(CH2)5NH—, —NH(CH2CH2O)kNH—, and —CO(CH2)5—, wherein h, i, j, and k are independently integers from 1 to 5; andm is an integer from 1 to 15. 8. The nucleic acid labeling compound of claim 7, wherein: L is N-alkyl amido; andM is —CH2—NR3—, wherein R3 is hydrogen or alkyl. 9. The nucleic acid labeling compound of claim 7, wherein: Y1 is hydrogen or OH;Z1 is —NH-L-(M)m-Q;L is —(CH2)nNHC(O)—, where n is an integer from 1 to 10;M is —NH(CH2)p—, where p is an integer from 1 to 10;R15 is hydrogen or methyl; andQ is biotin or a carboxyfluorescein. 10. The nucleic acid labeling compound of claim 9, wherein: Y1 is OH;R15 is hydrogen or methyl;-L-(M)m- is —(CH2)4NH—C(O)(CH2)5NH—; andQ is biotin or a carboxyfluorescein. 11. The nucleic acid labeling compound of claim 7, wherein: Y1 is —NH-L-(M)m-Q;Z1 is hydrogen or OH;L is selected from the group consisting of amido alkyl, functionalized alkyl, alkenyl alkyl, alkanoyl, and N-alkyl amido;M is —NH(CH2)p—, where p is an integer from 1 to 10;R15 is hydrogen or methyl; andQ is biotin or a carboxyfluorescein. 12. The nucleic acid labeling compound of claim 7, wherein: A is H or H4O9P3—;X1 is O;Y1 is hydrogen, OR9, wherein R9 is hydrogen or alkyl, or —O-L-(M)m-Q;Z1 is hydrogen, OR10, wherein R10 is hydrogen or alkyl, or —O-L-(M)m-Q;L is alkylene; andm is an integer from 1 to 10. 13. The nucleic acid labeling compound of claim 12, wherein: Y1 is hydrogen or OH;Z1 is —O-L-(M)m-Q;L is —(CH2)n—, where n is an integer from 1 to 12;M is selected from the group consisting of amino alkyl, —CO(CH2)5NH—, —CO—, —NH—, —CO(O)—, —CO(NH)—, —(CH2)iO—, —(CH2)jNH—, —C(O)(CH2)hO—, —CO(CH2)5NHCO(CH2)5NH—, —NH(CH2CH2O)kNH—, and —CO(CH2)5—, wherein h, i, j, and k are independently integers from 1 to 5;R15 is hydrogen or methyl; andQ is biotin or a carboxyfluorescein. 14. The nucleic acid labeling compound of claim 13, wherein: M is —NH—. 15. The nucleic acid labeling compound of claim 14, wherein: Y1 is OH;R15 is hydrogen or methyl;-L-(M)m- is —(CH2)6—NH—; andQ is biotin or a carboxyfluorescein. 16. The nucleic acid labeling compound of claim 7, wherein: Y1 is —O-L-(M)m-Q;Z1 is hydrogen or OH;L is —(CH2)n—, where n is an integer from 1 to 12;M is selected from the group consisting of amino alkyl, —CO(CH2)5NH—, —CO—, —NH—, —CO(O)—, —CO(NH)—, —(CH2)iO—, —(CH2)jNH—, —C(O)(CH2)hO—, —CO(CH2)5NHCO(CH2)5NH—, —NH(CH2CH2O)kNH—, and —CO(CH2)5—, wherein h, i, j, and k are independently integers from 1 to 5;R15 is hydrogen or methyl; andQ is biotin or a carboxyfluorescein. 17. The nucleic acid labeling compound of claim 16, wherein: Z1 is OH;R15 is hydrogen or methyl;-L-(M)m- is —(CH2)6—NH—; andQ is biotin or a carboxyfluorescein. 18. The nucleic acid labeling compound of claim 7, wherein: A is H or H4O9P3—;X1 is O;Y1 is hydrogen, OR9, wherein R9 is hydrogen or alkyl, or —S-L-(M)m-Q;Z1 is hydrogen, OR10, wherein R10 is hydrogen or alkyl, or —S-L-(M)m-Q;L is alkylene; andm is an integer from 1 to 10. 19. The nucleic acid labeling compound of claim 18, wherein: Y1 is hydrogen or OH;Z1 is —S-L-(M)m-Q;L is —S—(CH2)n—, where n is an integer from 1 to 10;M is selected from the group consisting of amino alkyl, —CO(CH2)5NH—, —CO—, —NH—, —CO(O)—, —CO(NH)—, —(CH2)iO—, —(CH2)jNH—, —C(O)(CH2)hO—, —CO(CH2)5NHCO(CH2)5NH—, —NH(CH2CH2O)kNH—, and —CO(CH2)5—, wherein h, i, j, and k are independently integers from 1 to 5;R15 is hydrogen or methyl; andQ is biotin or a carboxyfluorescein. 20. The nucleic acid labeling compound of claim 19, wherein: Y1 is OH;R15 is hydrogen or methyl;-L-(M)m- is —S—(CH2)2—NH—; andQ is biotin or a carboxyfluorescein. 21. The nucleic acid labeling compound of claim 7, wherein: Y1 is —S-L-(M)m-Q;Z1 is hydrogen or OH;L is —S—(CH2)n—, where n is an integer from 1 to 10;M is selected from the group consisting of amino alkyl, —CO(CH2)5NH—, —CO—, —NH—, —CO(O)—, —CO(NH)—, —(CH2)iO—, —(CH2)jNH—, —C(O)(CH2)hO—, —CO(CH2)5NHCO(CH2)5NH—, —NH(CH2CH2O)kNH—, and —CO(CH2)5—, wherein h, i, j, and k are independently integers from 1 to 5;R15 is hydrogen or methyl; andQ is biotin or a carboxyfluorescein. 22. The nucleic acid labeling compound of claim 21, wherein: Z1 is OH;R15 is hydrogen or methyl;-L-(M)m- is —S—(CH2)2—NH—; andQ is biotin or a carboxyfluorescein. 23. A nucleic acid derivative produced by the process of: attaching at least one nucleic acid to a support; andcoupling the at least one nucleic acid to the nucleic acid labeling compound of claim 1. 24. The nucleic acid derivative produced by the process of claim 23, wherein either a terminal transferase or a ligase performs the coupling step. 25. A hybridization product, comprising the nucleic acid derivative of claim 23 bound to a complementary probe. 26. The hybridization product of claim 25, wherein the complementary probe is attached to a glass chip.